Enhancing the use of Argos satellite data for home range and long distance migration studies of marine animals.
Accurately quantifying animals' spatial utilisation is critical for conservation, but has long remained an elusive goal due to technological impediments. The Argos telemetry system has been extensively used to remotely track marine animals, however location estimates are characterised by substantial spatial error. State-space models (SSM) constitute a robust statistical approach to refine Argos tracking data by accounting for observation errors and stochasticity in animal movement. Despite their wide use in ecology, few studies have thoroughly quantified the error associated with SSM predicted locations and no research has assessed their validity for describing animal movement behaviour. We compared home ranges and migratory pathways of seven hawksbill sea turtles (Eretmochelys imbricata) estimated from (a) highly accurate Fastloc GPS data and (b) locations computed using common Argos data analytical approaches. Argos 68(th) percentile error was <1 km for LC 1, 2, and 3 while markedly less accurate (>4 km) for LC ≤ 0. Argos error structure was highly longitudinally skewed and was, for all LC, adequately modelled by a Student's t distribution. Both habitat use and migration routes were best recreated using SSM locations post-processed by re-adding good Argos positions (LC 1, 2 and 3) and filtering terrestrial points (mean distance to migratory tracks ± SD = 2.2 ± 2.4 km; mean home range overlap and error ratio = 92.2% and 285.6 respectively). This parsimonious and objective statistical procedure however still markedly overestimated true home range sizes, especially for animals exhibiting restricted movements. Post-processing SSM locations nonetheless constitutes the best analytical technique for remotely sensed Argos tracking data and we therefore recommend using this approach to rework historical Argos datasets for better estimation of animal spatial utilisation for research and evidence-based conservation purposes.


Prevalence of Sexual Aggression Victimization and Perpetration in a Sample of Female and Male College Students in Turkey.
In Turkey, there is a shortage of studies on the prevalence of sexual aggression among young adults. The present study examined sexual aggression victimization and perpetration since the age of 15 in a convenience sample of N = 1,376 college students (886 women) from four public universities in Ankara, Turkey. Prevalence rates for different coercive strategies, victim-perpetrator constellations, and sexual acts were measured with a Turkish version of the Sexual Aggression and Victimization Scale (SAV-S). Overall, 77.6% of women and 65.5% of men reported at least one instance of sexual aggression victimization, and 28.9% of men and 14.2% of women reported at least one instance of sexual aggression perpetration. Prevalence rates of sexual aggression victimization and perpetration were highest for current or former partners, followed by acquaintances/friends and strangers. Alcohol was involved in a substantial proportion of the reported incidents. The findings are the first to provide systematic evidence on sexual aggression perpetration and victimization among college students in Turkey, including both women and men.


The role of the Birt-Hogg-Dubé protein in mTOR activation and renal tumorigenesis.
Birt-Hogg-Dubé (BHD) syndrome is a tumor-suppressor gene disorder characterized by skin tumors, cystic lung disease and renal cell carcinoma. Very little is known about the molecular pathogenesis of BHD. Clinical similarities between BHD and tuberous sclerosis complex (TSC) suggest that the BHD and TSC proteins may function within a common pathway. The TSC proteins inhibit the activity of the mammalian target of rapamycin complex 1 (TORC1), and in Schizosaccharomyces pombe, Bhd and Tsc1/Tsc2 have opposing roles in the regulation of amino-acid homeostasis. We report here that in mammalian cells, downregulation of BHD reduces the phosphorylation of ribosomal protein S6, an indicator of TORC1 activity. To determine whether folliculin, the product of the BHD gene, regulates mammalian target of rapamycin activity in vivo, we generated a mouse with targeted inactivation of the Bhd gene. The mice developed spontaneous oncocytic cysts and tumors composed of cells that resemble the renal cell carcinomas in BHD patients. The cysts and tumors had low levels of phospho-S6. Taken together, these data indicate that folliculin regulates the activity of TORC1, and suggest a new paradigm in which both inappropriately high and inappropriately low levels of TORC1 activity can be associated with renal tumorigenesis.


In-vitro assessment of antioxidant and antimicrobial activities of methanol extracts and essential oil of Thymus hirtus sp. algeriensis.
Owing to the complexity of the antioxidant materials and their mechanism of actions, it is obvious that no single testing method is capable of providing a comprehensive picture of the antioxidant profile. The essential oil of the Thymus specie may still possess other important activities in traditional medicine, it can be used in the treatment of fever and cough. This essential oil may also have an anticancer activity. The essential oils aerial parts hydrodistilled from Thymus hirtus sp. algeriensis, were characterised by GC/MS analysis and the methanolic extracts were chemically characterized by HPLC method. The essence of thyme was evaluated for its antioxidant and antibacterial activity. The Terpinen-4-ol are the principal class of metabolites (33.34%) among which 1.8-cineole (19.96%) and camphor (19.20%) predominate. In this study, quantitative values of antioxidant activity of crude methanolic extracts of Thymus hirtus sp. algeriensis were investigated. The essential oils was screened for their antibacterial activity against six common pathogenic microorganisms (Escherichia coli, Pseudomonas aeruginosa, Salmonella enteridis, Staphylococcus aureus, Bacillus subtilis and Listeria monocytogenes) by well diffusion method and agar dilution method (MIC). All the essences were found to inhibit the growth of both gram (+) and gram (-) bacteria organisms tested. These activities were correlated with the presence of phenolic compounds in active fractions. HPLC confirmed presence of phenolic compounds in methanol extracts. Methanol extracts and essential oils from aerial parts of Thymus hirtus sp. algeriensis, were examined for their potential as antioxidants. The technique for measuring antioxidant activity, which was developed using DPPH, ABTS and β-carotene bleaching, produced results as found in established literatures. The present results indicate clearly that methanol extracts and essential oils from Thymus hirtus sp. algeriensis possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants, also their essential oil have an antibacterial effect.


Rapid, pervasive genetic differentiation of urban white-footed mouse (Peromyscus leucopus) populations in New York City.
We investigated genetic diversity and structure of urban white-footed mouse, Peromyscus leucopus, populations in New York City (NYC) using variation at 18 microsatellite loci. White-footed mice are 'urban adapters' that occur at higher population densities as habitat fragments are reduced in area but have a limited ability to disperse through urbanized areas. We hypothesized that this combination of traits has produced substantial genetic structure but minimal loss of genetic variation over the last century in NYC. Allelic diversity and heterozygosity in 14 NYC populations were high, and nearly all of our NYC study sites contained genetically distinct populations of white-footed mice as measured by pairwise FST , assignment tests, and Bayesian clustering analyses performed by Structure and baps. Analysis of molecular variance revealed that genetic differences between populations separated by a few kilometres are more significant than differences between prehistorically isolated landmasses (i.e. Bronx, Queens, and Manhattan). Allele size permutation tests and lack of isolation by distance indicated that mutation and migration are less important than drift as explanations for structure in urban, fragmented P. leucopus populations. Peromyscus often exhibit little genetic structure over even regional scales, prompting us to conclude that urbanization is a particularly potent driver of genetic differentiation compared to natural fragmentation.


Evaluation of the linköping youth life experience scale.
The objective of this study was to investigate the psychometric properties of a newly developed instrument for potentially traumatic life events, the Linköping Youth Life Experience Scale (LYLES), and determine the benefits of including adverse childhood circumstances (ACCs) as factors in the evaluation. In addition, we wanted to investigate the difference between interpersonal and noninterpersonal traumatic events, the impact of ACCs, and the cumulative effects of these events on self-reported symptoms of dissociation, depression, and anxiety. Adolescents from the normative population (n = 188) answered the questionnaire LYLES and also the Dissociation-Questionnaire-Sweden and Hospital Anxiety and Depression Scale. The results showed that LYLES was stable, with test-retest r = 0.79 and kappa item per item ranging between k = 0.44 and 1.0. ACCs contributed independently to the explanation of symptoms explaining them better than potentially traumatic events alone, particularly for boys where the impact of ACCs exceeded the impact of events. The conclusions are that LYLES displayed satisfactory psychometric properties and that ACCs seem to be a valuable addition to an instrument to evaluate potentially traumatic events.


Prereplicative repair of oxidized bases in the human genome is mediated by NEIL1 DNA glycosylase together with replication proteins.
Base oxidation by endogenous and environmentally induced reactive oxygen species preferentially occurs in replicating single-stranded templates in mammalian genomes, warranting prereplicative repair of the mutagenic base lesions. It is not clear how such lesions (which, unlike bulky adducts, do not block replication) are recognized for repair. Furthermore, strand breaks caused by base excision from ssDNA by DNA glycosylases, including Nei-like (NEIL) 1, would generate double-strand breaks during replication, which are not experimentally observed. NEIL1, whose deficiency causes a mutator phenotype and is activated during the S phase, is present in the DNA replication complex isolated from human cells, with enhanced association with DNA in S-phase cells and colocalization with replication foci containing DNA replication proteins. Furthermore, NEIL1 binds to 5-hydroxyuracil, the oxidative deamination product of C, in replication protein A-coated ssDNA template and inhibits DNA synthesis by DNA polymerase δ. We postulate that, upon encountering an oxidized base during replication, NEIL1 initiates prereplicative repair by acting as a "cowcatcher" and preventing nascent chain growth. Regression of the stalled replication fork, possibly mediated by annealing helicases, then allows lesion repair in the reannealed duplex. This model is supported by our observations that NEIL1, whose deficiency slows nascent chain growth in oxidatively stressed cells, is stimulated by replication proteins in vitro. Furthermore, deficiency of the closely related NEIL2 alone does not affect chain elongation, but combined NEIL1/2 deficiency further inhibits DNA replication. These results support a mechanism of NEIL1-mediated prereplicative repair of oxidized bases in the replicating strand, with NEIL2 providing a backup function.


Health symptoms and the work environment in four nonproblem United States office buildings.
The objective of this study was to quantify health symptom reports in four "nonproblem" buildings and to assess the relationship between symptoms and air quality measures, workstation characteristics, and psychosocial aspects of the workplace. Environmental sampling was conducted in four office buildings occupied by employees working for the state of Washington in March of 1992. A questionnaire was concurrently administered to building occupants. While measured contaminant levels were low, symptoms were frequent. Fifty-five percent of the 646 respondents reported recent symptoms which affected the eyes, nose, or throat and improved when away from work. Symptoms were not associated with measured contaminant levels, but, rather, with perceptions about air movement, dryness, odors, and noise. Psychosocial factors were less strongly associated with symptoms. Even in nonproblem buildings, symptom reports can be frequent and may represent overall satisfaction with the work environment. In response to symptoms ascribed to air quality problems, it may be appropriate to address employee perceptions regarding the work environment in addition to evaluating environmental characteristics relating to chemicals, biological contamination, air movement, temperature, and humidity.


Quantitative evaluation of protein expression as a function of tissue microarray core diameter: is a large (1.5 mm) core better than a small (0.6 mm) core?
Tissue microarrays (TMAs) have emerged as a high-throughput technology for protein evaluation in large cohorts. This technique allows maximization of tissue resources by analysis of sections from 0.6-mm to 1.5-mm core "biopsies" of standard formalin-fixed, paraffin-embedded tissue blocks and by the processing of hundreds of cases arrayed on a single recipient block in an identical manner. To assess the expression of a series of biomarkers as a function of core size. Although pathologists frequently feel better if larger core sizes are used, there is no evidence in the literature showing that large cores are better (or worse) than small cores for assessment of TMAs. Estrogen receptor, HER2/neu, epidermal growth factor receptor, STAT3, mTOR, and phospho-p70 S6 kinase were measured by immunofluorescence with automated quantitative analysis. One random 0.6-mm field (one 0.6-mm spot) was compared to 6 to 12 fields per spot, representing 1-mm and 1.5-mm cores, for 3 different tumor types. We show that measurement of a single random 0.6-mm spot was comparable to analysis of the whole 1-mm or 1.5-mm spot (Pearson R coefficient varying from 0.87-0.98) for all markers tested. Since TMA technology is now being used in all phases of biomarker development, this work shows that TMAs with 0.6-mm cores are as representative as those with any common larger core size for optimization of standardized experimental conditions. Given that a greater number of 0.6-cores can be arrayed in a single master block, use of this core size allows increased throughput and decreased cost.


Dual-source CT in step-and-shoot mode: noninvasive coronary angiography with low radiation dose.
To prospectively investigate computed tomographic (CT) image quality parameters by using different protocols and to calculate radiation dose estimates for noninvasive coronary angiography performed with dual-source CT in the step-and-shoot (SAS) mode. This study was local ethics board approved; written informed consent was obtained from all patients. In the preliminary portion of the study, 40 patients underwent CT coronary angiography in the SAS mode: at 100 kV (protocol A) in 22 patients with a body mass index (BMI) of less than 25 kg/m(2) and at 120 kV (protocol B) in 18 patients with a BMI of 25-30 kg/m(2). Both protocols involved use of an attenuation-based tube current and 1 mL of contrast material per kilogram of body weight. The final portion of the study involved 50 additional patients: 21 patients with a BMI of 25-30 kg/cm(2) assigned to protocol B and 29 patients with a BMI of less than 25 kg/cm(2) assigned to protocol C, which was performed with 100 kV, an attenuation-based tube current, and a reduced contrast material dose of 0.8 mL/kg. Image quality was independently assessed. Attenuation in the aorta and coronary arteries and image noise were measured. Radiation dose was estimated. Mean image noise was similar with protocols A and B. Mean attenuation in the aorta and coronary arteries with protocol A (444 HU) was significantly (P < .001) higher than that with protocol B (358 HU). The reduced contrast material dose in protocol C yielded attenuation similar to that with protocol B. Diagnostic image quality was achieved with all protocols in 1237 (97.9%) of 1264 coronary segments. No significant differences in image quality between the 100- and 120-kV protocols were found. Mean heart rate had a significant effect on motion artifacts (area under receiver operating characteristic curve [AUC] = 0.818; 95% confidence interval [CI]: 0.723, 0.892; P < .001), whereas heart rate variability had a significant effect on stair-step artifacts (AUC = 0.79; 95% CI: 0.687, 0.865; P < .001). The mean estimated effective dose was 1.2 mSv +/- 0.2 for protocols A and C and 2.6 mSv +/- 0.5 for protocol B. Dual-source SAS-mode CT coronary angiography yielded diagnostic image quality for 97.9% of coronary segments at a low radiation dose.


Bacterial inclusion bodies contain amyloid-like structure.
Protein aggregation is a process in which identical proteins self-associate into imperfectly ordered macroscopic entities. Such aggregates are generally classified as amorphous, lacking any long-range order, or highly ordered fibrils. Protein fibrils can be composed of native globular molecules, such as the hemoglobin molecules in sickle-cell fibrils, or can be reorganized beta-sheet-rich aggregates, termed amyloid-like fibrils. Amyloid fibrils are associated with several pathological conditions in humans, including Alzheimer disease and diabetes type II. We studied the structure of bacterial inclusion bodies, which have been believed to belong to the amorphous class of aggregates. We demonstrate that all three in vivo-derived inclusion bodies studied are amyloid-like and comprised of amino-acid sequence-specific cross-beta structure. These findings suggest that inclusion bodies are structured, that amyloid formation is an omnipresent process both in eukaryotes and prokaryotes, and that amino acid sequences evolve to avoid the amyloid conformation.


Evidence utilisation project: Management of inadvertent perioperative hypothermia. The challenges of implementing best practice recommendations in the perioperative environment.
The prevention of inadvertent perioperative hypothermia (IPH) remains an important issue in perioperative healthcare. The aims of this project were to: (i) assess current clinical practice in the management of IPH and (ii) promote best practice in the management of IPH in adult operating theatres. This project from August 2010 to March 2012 utilised a system of audit and feedback to implement best practice recommendations. Data were collected via chart audits against criteria developed from best practice recommendations for managing IPH. Evidence-based best practices, such as consistent temperature monitoring and patient warming, were implemented using multifaceted interventions. Perioperative records for 73 patients (baseline) and 72 patients (post-implementation) were audited. Post-implementation audit showed an increase in patients with temperatures >36°C admitted to the post-anaesthetic care unit (PACU) (8%) and discharged from PACU (28%). The percentage of patients receiving preoperative temperature monitoring increased (38%); however, low levels of intraoperative monitoring remained (31% of patients with surgery of 30 min or longer duration). Small increases were found in patient warming of 5% intraoperatively and 8% postoperatively. Preoperative warming was not successfully implemented during this phase of the project. Temperature monitoring, warming and rates of normothermia improved; however, barriers to best practice of IPH management were experienced, which negatively impacted on the project. Further stages of implementation and audit were added to further address IPH management in this department.


Performance of Prognostic Risk Scores in Chronic Heart Failure Patients Enrolled in the European Society of Cardiology Heart Failure Long-Term Registry.
This study compared the performance of major heart failure (HF) risk models in predicting mortality and examined their utilization using data from a contemporary multinational registry. Several prognostic risk scores have been developed for ambulatory HF patients, but their precision is still inadequate and their use limited. This registry enrolled patients with HF seen in participating European centers between May 2011 and April 2013. The following scores designed to estimate 1- to 2-year all-cause mortality were calculated in each participant: CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality), GISSI-HF (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure), MAGGIC (Meta-analysis Global Group in Chronic Heart Failure), and SHFM (Seattle Heart Failure Model). Patients with hospitalized HF (n = 6,920) and ambulatory HF patients missing any variable needed to estimate each score (n = 3,267) were excluded, leaving a final sample of 6,161 patients. At 1-year follow-up, 5,653 of 6,161 patients (91.8%) were alive. The observed-to-predicted survival ratios (CHARM: 1.10, GISSI-HF: 1.08, MAGGIC: 1.03, and SHFM: 0.98) suggested some overestimation of mortality by all scores except the SHFM. Overprediction occurred steadily across levels of risk using both the CHARM and the GISSI-HF, whereas the SHFM underpredicted mortality in all risk groups except the highest. The MAGGIC showed the best overall accuracy (area under the curve [AUC] = 0.743), similar to the GISSI-HF (AUC = 0.739; p = 0.419) but better than the CHARM (AUC = 0.729; p = 0.068) and particularly better than the SHFM (AUC = 0.714; p = 0.018). Less than 1% of patients received a prognostic estimate from their enrolling physician. Performance of prognostic risk scores is still limited and physicians are reluctant to use them in daily practice. The need for contemporary, more precise prognostic tools should be considered.


Perinatal exposure to low doses of PCB 153 and PCB 126 affects maternal and neonatal immunity in goat kids.
Pregnant does (10 goats/group) were dosed orally either with polychlorinated biphenyl (PCB) 153 (98 microg/kg body weight/d) or PCB 126 (ng/kg body weight/d) dissolved in corn oil or with corn oil only (control group) from gestation day (GD) 60 until delivery. An additional group (n = 5) of pregnant does received the synthetic estrogen diethylstilbestrol (DES; 0.4 microg/kg body weight/d) by intramuscular injection using the same treatment schedule as for the PCB groups. Blood samples for immune analysis were collected at wk 0, 1, 2, 4, 6, and 8 of age. The effects of perinatal PCB exposure on postnatal humoral immune responses were examined by assessing the levels of total immunoglobulin G (IgG) and immunoglobulins to specific microbes at wk 0, 1, 2, 4, 6, and 8 of age, and immune responses following immunization of kids at 2 wk of age. PCB 153 exposure suppressed maternal and neonatal immunity, as demonstrated by reduced transfer of maternal IgG and specific antibodies to the environmental microbes Arcanobacterium pyogenes, Mannheimia haemolytica, and reovirus (REO-1). Furthermore, PCB 153 reduced the level of maternal antibodies to Mycobacterium avium paratuberculosis and equine influenza virus (EIV-1) in the newborn kids. The antibody response against EIV-1 was significantly higher in PCB 153-exposed kids 2 wk following immunization. PCB 126 exposure reduced the levels of maternal antibodies to REO-1. In contrast, gestational exposure to PCB 126 increased the concentrations of maternal antibodies to tetanus toxoid. No differences from controls in plasma total IgG levels at birth or colostrum IgG concentrations were observed in the PCB 126-treated does. However, a significant reduction in IgG levels from GD 60 until delivery was found in this group. Gestational exposure to DES reduced the concentrations of maternal antibodies against A. pyogenes, M. haemolytica, M. avium Paratuberculosis, and REO-1. These results suggest that perinatal exposure to low doses of PCB 126 and PCB 153 affects the maternal immunity in kids. The difference in responses between PCB 126 and PCB 153 treatment groups may strengthen the hypothesis that PCBs mediate immunotoxic effects through both AhR-dependent and -independent mechanisms. The observation that the effects produced by PCB 153 resembled those produced by DES raises the question of whether this congener may modulate immunity by estrogenic mechanisms.


A perceptual learning investigation of the pitch elicited by amplitude-modulated noise.
Noise that is amplitude modulated at rates ranging from 40 to 850 Hz can elicit a sensation of pitch. Here, the processing of this temporally based pitch was investigated using a perceptual-learning paradigm. Nine listeners were trained (1 hour per day for 6-8 days) to discriminate a standard rate of sinusoidal amplitude modulation (SAM) from a faster rate in a single condition (150 Hz SAM rate, 5 kHz low-pass carrier). All trained listeners improved significantly on that condition. These trained listeners subsequently showed no more improvement than nine untrained controls on pure-tone and rippled-noise discrimination with the same pitch, and on SAM-rate discrimination with a 30 Hz rate, although they did show some improvement with a 300 Hz rate. In addition, most trained, but not control, listeners were worse at detecting SAM at 150 Hz after, compared to before training. These results indicate that listeners can learn to improve their ability to discriminate SAM rate with multiple-hour training and that the mechanism that is modified by learning encodes (1) the pitch of SAM noise but not that of pure tones and rippled noise, (2) different SAM rates separately, and (3) differences in SAM rate more effectively than cues for SAM detection.


Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells.
The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50(th) percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually.


System redesign of the immunization supply chain: Experiences from Benin and Mozambique.
Evidence suggests that immunization supply chains are becoming outdated and unable to deliver needed vaccines due to growing populations and new vaccine introductions. Redesigning a supply chain could result in meeting current demands. The Ministries of Health in Benin in Mozambique recognized known barriers to the immunization supply chain and undertook a system redesign to address those barriers. Changes were made to introduce an informed push system while consolidating storage points, introducing transport loops, and increasing human resource capacity for distribution. Evaluations were completed in each country. Evaluation in each country indicated improved performance of the supply chain. The Effective Vaccine Management (EVM) assessment in Benin documented notable improvements in the distribution criteria of the tool, increasing from 40% to 100% at the district level. In Mozambique, results showed reduced stockouts at health facility level from 79% at baseline to less than 1% at endline. Coverage rates of DTP3 also increased from 68.9% to 92.8%. Benin and Mozambique are undertaking system redesign in order to respond to constraints identified in the vaccine supply chain. Results and learnings show improvements in supply chain performance and make a strong case for system redesign. These countries demonstrate the feasibility of system redesign for other countries considering how to address outdated supply chains.


Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK.
Inflammation is central to the pathogenesis of many diseases. Supplementation with selenium and coenzyme Q10 has been shown to reduce cardiovascular mortality, and increase cardiac function in elderly persons with a low intake of selenium. There are indications that one of the mechanisms of this positive effect is a decrease in inflammation. Osteopontin, osteoprotegerin, sTNF receptor 1, sTNF receptor 2 and the tumor necrosis factor-like weak inducer of apoptosis called TWEAK, were determined in plasma after 6 months and 42 months in 219 community-living elderly persons, of whom 119 received supplements of selenium (200 μg/day) and coenzyme Q10 (200 mg/day), and 101 received a placebo. Repeated measures of variance were used to evaluate the levels, and the results were validated through ANCOVA analyses with adjustments for important covariates. Significantly lower concentrations of four of the five biomarkers for inflammation were observed as a result of the intervention with the supplements. Only TWEAK did not show significant differences. In this sub-analysis of the intervention with selenium and coenzyme Q10 or placebo in an elderly community-living population, biomarkers for inflammation were evaluated. A significantly lower concentration in four of the five biomarkers tested could be demonstrated as a result of the supplementation, indicating a robust effect on the inflammatory system. The decrease in inflammation could be one of the mechanisms behind the positive clinical results on reduced cardiovascular morbidity and mortality reported earlier as a result of the intervention. The study is small and should be regarded as hypothesis-generating, but nonetheless adds important data about mechanisms presently known to increase the risk of clinical effects such as reduced cardiovascular mortality, increased cardiac function and better health-related quality of life scoring, as previously demonstrated in the active treatment group . The intervention study was registered at Clinicaltrials.gov, and has the identifier NCT01443780 and registered on 09/30/2011.


Direct analysis of beta-adrenergic receptor subtypes on intact adult ventricular myocytes of the rat.
beta 1- and beta 2-Adrenergic receptors co-exist in the adult rat ventricle. We have employed radioligand binding and cell purification techniques to determine the cellular origin of these receptors. The beta-adrenergic antagonist ligand (+/-)-[125I] iodocyanopindolol binds to 2 X 10(5) receptors per purified adult rat cardiomyocyte, with a dissociation constant of 70 pM. The subtype-selective antagonists betaxolol (beta 1), practolol (beta 1), and zinterol (beta 2) compete for [125I]iodocyanopindolol-binding sites on intact myocytes in monophasic manners with dissociation constants of 46, 845, and 923 nM, respectively. [125I]iodocyanopindolol binding to membranes prepared from nonmyocyte elements of rat ventricle occurs with a dissociation constant of 43 pM and a capacity of 88 fmol/mg membrane protein. Computer analysis of competition of [125I]iodocyanopindolol binding by betaxolol, practolol, and zinterol in nonmyocyte membranes demonstrates biphasic curves that comprise binding to both beta 1- and beta 2-receptors. These data demonstrate that purified adult ventricular myocytes possess only beta 1-receptors, and that the beta 2-receptors found in rat ventricle are located on nonmyocyte cell types.


Retrieval practice as an effective memory strategy in children and adolescents with traumatic brain injury.
To investigate whether retrieval practice (RP) is a more effective memory strategy than restudy in children and adolescents with traumatic brain injury (TBI). Three × two within-subjects experiment: 3 (learning condition: massed restudy [MR], spaced restudy [SR], retrieval practice [RP]) × 2 (stimulus type: verbal paired associates [VPAs] and face-name pairs [FNPs]). The dependent measure was delayed recall of VPAs and FNPs. Subacute pediatric neurorehabilitation center. Pediatric survivors of TBI (N=15) aged 8 to 16 years with below-average memory. During RP, participants were quizzed on to-be-learned information (VPAs and FNPs) shortly after it was presented, such that they practiced retrieval during the learning phase. MR consisted of repeated restudy (tantamount to cramming). SR consisted of restudy trials separated in time (ie, distributed learning). Delayed recall of 24 VPAs and 24 FNPs after a 25-minute delay. VPAs and FNPs were equally divided across 3 learning conditions (16 per condition). There was a large main effect of learning condition on delayed recall (P<.001; ηp(2)=.84), with better mean recall of VPAs and FNPs studied through RP (6.23±1.39) relative to MR (3.60±1.53; P<.001) and SR (4.77±1.39; P<.001). Moreover, RP was the single best learning strategy for every participant. Memory problems and related academic learning difficulties are common after pediatric TBI. Herein, we identify RP as a promising and simple strategy to support learning and improve memory in children and adolescents with TBI. Our experimental findings were quite robust and set the stage for subsequent randomized controlled trials of RP in pediatric TBI.


Born to Run? Quantifying the Balance of Prior Bias and New Information in Prey Escape Decisions.
Animal behaviors can often be challenging to model and predict, though optimality theory has improved our ability to do so. While many qualitative predictions of behavior exist, accurate quantitative models, tested by empirical data, are often lacking. This is likely due to variation in biases across individuals and variation in the way new information is gathered and used. We propose a modeling framework based on a novel interpretation of Bayes's theorem to integrate optimization of energetic constraints with both prior biases and specific sources of new information gathered by individuals. We present methods for inferring distributions of prior biases within populations rather than assuming known priors, as is common in Bayesian approaches to modeling behavior, and for evaluating the goodness of fit of overall model descriptions. We apply this framework to predict optimal escape during predator-prey encounters, based on prior biases and variation in what information prey use. Using this approach, we collected and analyzed data characterizing white-tailed deer (Odocoileus virginianus) escape behavior in response to human approaches. We found that distance to predator alone was not sufficient to predict deer flight response and show that the inclusion of additional information is necessary. We also compared differences in the inferred distributions of prior biases across different populations and discuss the possible role of human activity in influencing these distributions.


Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice.
Autosomal dominant hypophosphatemic rickets (ADHR) is unique among the disorders involving Fibroblast growth factor 23 (FGF23) because individuals with R176Q/W and R179Q/W mutations in the FGF23 (176)RXXR(179)/S(180) proteolytic cleavage motif can cycle from unaffected status to delayed onset of disease. This onset may occur in physiological states associated with iron deficiency, including puberty and pregnancy. To test the role of iron status in development of the ADHR phenotype, WT and R176Q-Fgf23 knock-in (ADHR) mice were placed on control or low-iron diets. Both the WT and ADHR mice receiving low-iron diet had significantly elevated bone Fgf23 mRNA. WT mice on a low-iron diet maintained normal serum intact Fgf23 and phosphate metabolism, with elevated serum C-terminal Fgf23 fragments. In contrast, the ADHR mice on the low-iron diet had elevated intact and C-terminal Fgf23 with hypophosphatemic osteomalacia. We used in vitro iron chelation to isolate the effects of iron deficiency on Fgf23 expression. We found that iron chelation in vitro resulted in a significant increase in Fgf23 mRNA that was dependent upon Mapk. Thus, unlike other syndromes of elevated FGF23, our findings support the concept that late-onset ADHR is the product of gene-environment interactions whereby the combined presence of an Fgf23-stabilizing mutation and iron deficiency can lead to ADHR.


Fetal and placental vascular tumors: persistent fetal hyperdynamic status predisposes to poorer long-term neurodevelopmental outcome.
To evaluate the association between fetal hemodynamic changes seen in the presence of vascular tumors of fetal or placental origin and risk of adverse pregnancy outcome. All cases of placental chorioangioma, sacrococcygeal teratoma and pulmonary sequestration during a 10-year period were included. Ultrasound data and pregnancy and long-term neurodevelopmental outcomes were assessed in this cohort. A survival analysis was performed to assess the relationship between the cardiovascular profile score (CVPS) and adverse pregnancy outcome. There were 56 fetal or placental tumors, including 28 chorioangiomas, 10 sacrococcygeal teratomas and 18 pulmonary sequestrations, diagnosed at a median gestation of 23 + 3 weeks. Abnormal CVPS (≤ 8) was seen in 30% of sacrococcygeal teratomas and in 46% of chorioangiomas, but in none of the pulmonary sequestration cases. Adverse pregnancy outcome occurred in 11 cases (three stillbirths, three neonatal deaths and five cases of developmental delay) and only in those cases in which the tumors were associated with a CVPS of ≤ 8. Certain fetal and placental vascular tumors are associated with cardiac dysfunction in fetal life. When the CVPS is low (≤ 8), these cases are at increased risk of both fetal/neonatal demise as well as overt long-term neurodevelopmental disability. The long-term neurodevelopmental outcome should be formally and prospectively assessed in cases of fetal and placental vascular tumors.


Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes.
Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC. A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicities were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were calculated with the Kaplan-Meier method. Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding. Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings.


Future perspectives in functional neuroimaging in stroke recovery.
Neurological damage and stroke in particular is the leading cause of long-term disability worldwide. Recovery of function after stroke is a consequence of many factors including resolution of oedema and survival of the ischaemic penumbra. In addition, there is a growing interest in how reorganisation of the surviving tissue might subserve the improvements in function that are commonly seen over weeks, months, and sometimes years after stroke. Noninvasive techniques such as functional magnetic resonance imaging, electroencephalography, magnetoencephalography and transcranial magnetic stimulation allow the study of this reorganisation in humans. Currently, results suggest that functionally relevant reorganisation does occur in cerebral networks in human stroke patients. This reorganisation can only occur in structurally and functionally intact brain regions. Because these vary depending on the location of the infarction, it is likely that different therapeutic strategies will be required to promote reorganisation depending on residual functional anatomy. This review maps out the attempts to describe functionally relevant adaptive changes in the human brain following focal damage. A greater understanding of how these changes are related to the recovery process will facilitate the development of novel therapeutic techniques designed to minimise impairment based on neurobiological principles and how to target these treatments to individual patients.


Evolution of breast cancer screening in countries with intermediate and increasing incidence of breast cancer.
Few studies have been published regarding the practice of breast cancer screening in Asian countries. The present study illustrates how the health policy for breast cancer screening has evolved in Taiwan from selective mammographic screening within a high-risk group, firstly to a programme of physical examination by public health nurses, and finally to a two-stage breast cancer screening programme, with a risk assessment followed by mammography for those at moderate to high risk. Breast cancer screening has evolved from 1995 to 2004 in Taiwan in three stages: (1) selective screening for breast cancer with mammography, ultrasound and physical examination only in first-degree relatives of breast cancer cases (1995-1998); (2) a programme of mass screening (1999-2001) with physical examination by public health nurses; and (3) two-stage breast cancer screening with a risk factor questionnaire and mammography for those deemed at moderate-to-high risk (2002-2004). The questionnaire was based on significant risk factors in a previous epidemiological study, in conjunction with the physical examination programme, a risk score was constructed from the logistic regression coefficients from the previous study, and women with a score above the median in the previous epidemiological study were assigned to mammography. Two-stage mammography screening had the most favourable results compared with the two previous screening regimes. It had a positive predictive value of recall after mammography of 14%, compared with 8% for selective screening and 2% for physical examination. Of screen-detected cancers in the two-stage programme, 71% were either ductal carcinoma in situ or stage T1, compared with 61% for selective screening and 60% for physical examination. The area under the receiver operating characteristic curve was 71% for the two-stage programme. For a low- to medium-risk country such as Taiwan, two-stage screening has acceptable parameters of recall and cancer detection, and compares well with other screening strategies.


Activity-based funding of hospitals and its impact on mortality, readmission, discharge destination, severity of illness, and volume of care: a systematic review and meta-analysis.
Activity-based funding (ABF) of hospitals is a policy intervention intended to re-shape incentives across health systems through the use of diagnosis-related groups. Many countries are adopting or actively promoting ABF. We assessed the effect of ABF on key measures potentially affecting patients and health care systems: mortality (acute and post-acute care); readmission rates; discharge rate to post-acute care following hospitalization; severity of illness; volume of care. We undertook a systematic review and meta-analysis of the worldwide evidence produced since 1980. We included all studies reporting original quantitative data comparing the impact of ABF versus alternative funding systems in acute care settings, regardless of language. We searched 9 electronic databases (OVID MEDLINE, EMBASE, OVID Healthstar, CINAHL, Cochrane CENTRAL, Health Technology Assessment, NHS Economic Evaluation Database, Cochrane Database of Systematic Reviews, and Business Source), hand-searched reference lists, and consulted with experts. Paired reviewers independently screened for eligibility, abstracted data, and assessed study credibility according to a pre-defined scoring system, resolving conflicts by discussion or adjudication. Of 16,565 unique citations, 50 US studies and 15 studies from 9 other countries proved eligible (i.e. Australia, Austria, England, Germany, Israel, Italy, Scotland, Sweden, Switzerland). We found consistent and robust differences between ABF and no-ABF in discharge to post-acute care, showing a 24% increase with ABF (pooled relative risk = 1.24, 95% CI 1.18-1.31). Results also suggested a possible increase in readmission with ABF, and an apparent increase in severity of illness, perhaps reflecting differences in diagnostic coding. Although we found no consistent, systematic differences in mortality rates and volume of care, results varied widely across studies, some suggesting appreciable benefits from ABF, and others suggesting deleterious consequences. Transitioning to ABF is associated with important policy- and clinically-relevant changes. Evidence suggests substantial increases in admissions to post-acute care following hospitalization, with implications for system capacity and equitable access to care. High variability in results of other outcomes leaves the impact in particular settings uncertain, and may not allow a jurisdiction to predict if ABF would be harmless. Decision-makers considering ABF should plan for likely increases in post-acute care admissions, and be aware of the large uncertainty around impacts on other critical outcomes.


Abundance and dynamics of filamentous fungi in the complex ambrosia gardens of the primitively eusocial beetle Xyleborinus saxesenii Ratzeburg (Coleoptera: Curculionidae, Scolytinae).
Insect fungus gardens consist of a community of interacting microorganisms that can have either beneficial or detrimental effects to the farmers. In contrast to fungus-farming ants and termites, the fungal communities of ambrosia beetles and the effects of particular fungal species on the farmers are largely unknown. Here, we used a laboratory rearing technique for studying the filamentous fungal garden community of the ambrosia beetle, Xyleborinus saxesenii, which cultivates fungi in tunnels excavated within dead trees. Raffaelea sulfurea and Fusicolla acetilerea were transmitted in spore-carrying organs by gallery founding females and established first in new gardens. Raffaelea sulfurea had positive effects on egg-laying and larval numbers. Over time, four other fungal species emerged in the gardens. Prevalence of one of them, Paecilomyces variotii, correlated negatively with larval numbers and can be harmful to adults by forming biofilms on their bodies. It also comprised the main portion of garden material removed from galleries by adults. Our data suggest that two mutualistic, several commensalistic and one to two pathogenic filamentous fungi are associated with X. saxesenii. Fungal diversity in gardens of ambrosia beetles appears to be much lower than that in gardens of fungus-culturing ants, which seems to result from essential differences in substrates and behaviours.


Synthesis of 3,3-disubstituted oxindoles by one-pot integrated Brønsted base-catalyzed trichloroacetimidation of 3-hydroxyoxindoles and Brønsted acid-catalyzed nucleophilic substitution reaction.
Treatment of 3-hydroxyoxindoles with trichloroacetonitrile (1.3 equiv.) and a catalytic amount of DBU (0.1 equiv.) followed by addition of nucleophiles (1.5 equiv.) and diphenylphosphoric acid (0.2 equiv.) afforded the 3,3-disubstituted oxindoles in good to excellent yields. DFT computations supported the notion that the reaction went through the 1-alkyl-2-oxo-2H-indol-1-ium intermediate.


19F NMR study of the equilibria and dynamics of the Al3+/F- system.
A careful reinvestigation by high-field 19F NMR (470 MHz) spectroscopy has been made of the Al3+/F- system in aqueous solution under carefully controlled conditions of pH, concentration, ionic strength (I), and temperature. The 19F NMR spectra show five distinct signals at 278 K and I = 0.6 M (TMACl) which have been attributed to the complexes AlFi(3-i)+(aq) with i < or = 5. There was no need to invoke AlFi(OH)j(3-i-j)+ mixed complexes in the model under our experimental conditions (pH < or = 6.5), nor was any evidence obtained for the formation of AlF6(3-)(aq) at very high ratios of F-/Al3+. The stepwise equilibrium constants obtained for the complexes by integration of the 19F signals are in good agreement with literature data given the differences in medium and temperature. In I = 0.6 M TMACl at 278 K and in I = 3 M KCl at 298 K the log Ki values are 6.42, 5.41, 3.99, 2.50, and 0.84 (for species i = 1-5) and 6.35, 5.25, and 4.11 (for species i = 1-3), respectively. Disappearance of the 19F NMR signals under certain conditions was shown to be due to precipitation. Certain 19F NMR signals exhibit temperature- and concentration-dependent exchange broadening. Detailed line shape analysis of the spectra and magnetization transfer measurements indicate that the kinetics are dominated by F- exchange rather than complex formation. The detected reactions and their rate constants are AlF2(2+) + *F- reversible AlF*F2+ + F- (k02 = (1.8 +/- 0.3) x 10(6) M-1 s-1), AlF3(0) + *F- reversible AlF2*F0 + F- (k03 = (3.9 +/- 0.9) x 10(6) M-1 s-1), and AlF3(0) + H*F reversible AlF2*F0 + HF (kH03 = (6.6 +/- 0.5) x 10(4) M-1 s-1). The rates of these exchange reactions increase markedly with increasing F- substitution. Thus, the reactions of AlF2+(aq) were too inert to be detected even on the T1 NMR time scale, while some of the reactions of AlF3(0)(aq) were fast, causing large line broadening. The ligand exchange appears to follow an associative interchange mechanism. The cis-trans isomerization of AlF2+(aq), consistent with octahedral geometry for that complex, is slowed sufficiently to be observed at temperatures around 270 K. Difference between the Al3+/F- system and the much studied Al3+/OH- system are briefly commented on.


Production, purification and characterization of the catalytic domain of glucoamylase from Aspergillus niger.
The catalytic domain of glucoamylases G1 and G2 from Aspergillus niger is produced in vitro in high yield by limited proteolysis using either subtilisin Novo or subtilisin Carlsberg. Purification by affinity chromatography on an acarbose-Sepharose column followed by ion-exchange chromatography on HiLoad Q-Sepharose leads to separation of a number of structurally closely related forms of domain. The cleavage occurs primarily between Val-470 and Ala-471 as indicated by C-terminal sequencing, whereas the N-terminus is intact. Subtilisin Carlsberg, in addition, produces a type of domain which is hydrolysed before Ser-444, an O-glycosylated residue. This leaves the fragment Ser-444-Val-470 disulphide-bonded to the large N-terminal part of the catalytic domain. Subtilisin Novo, in contrast, tends to yield a minor fraction of forms extending approx. 30-40 amino-acid residues beyond Val-470. The thermostability is essentially the same for the single-chain catalytic domain and the original glucoamylases G1 and G2, whereas the catalytic domain cut between Ser-443 and Ser-444 is less thermostable. For both types of domain the kinetic parameters, Km and kcat., for hydrolysis of maltose are very close to the values found for glucoamylases G1 and G2.


Volumetric absorptive microsampling: its use in COVID-19 research and testing.
COVID-19 led to changes in the way blood samples are collected. As societies were isolated to control viral spread, access to facilities became limited. Remote sample collection with a volumetric microsampling approach, using Mitra® devices based on VAMS® technology, proved to be highly effective. It allowed people to collect high-quality samples at home and post them to a laboratory. This enabled scientists to conduct large serosurveillance studies, with results showing that seroprevalence of COVID-19 was higher than initially expected. Furthermore, remote microsampling studies by several institutions were conducted to measure the relationship between antigen levels and antibody response and duration. VAMS technology was also used in COVID-19 clinical trials. In summary, the independent research reviewed in this paper proved that VAMS is an effective sample collection alternative.


Megraft: a software package to graft ribosomal small subunit (16S/18S) fragments onto full-length sequences for accurate species richness and sequencing depth analysis in pyrosequencing-length metagenomes and similar environmental datasets.
Metagenomic libraries represent subsamples of the total DNA found at a study site and offer unprecedented opportunities to study ecological and functional aspects of microbial communities. To examine the depth of a community sequencing effort, rarefaction analysis of the ribosomal small subunit (SSU/16S/18S) gene in the metagenome is usually performed. The fragmentary, non-overlapping nature of SSU sequences in metagenomic libraries poses a problem for this analysis, however. We introduce a software package - Megraft - that grafts SSU fragments onto full-length SSU sequences, accounting for observed and unobserved variability, for accurate assessment of species richness and sequencing depth in metagenomics endeavors.


KCB-Net: A 3D knee cartilage and bone segmentation network via sparse annotation.
Knee cartilage and bone segmentation is critical for physicians to analyze and diagnose articular damage and knee osteoarthritis (OA). Deep learning (DL) methods for medical image segmentation have largely outperformed traditional methods, but they often need large amounts of annotated data for model training, which is very costly and time-consuming for medical experts, especially on 3D images. In this paper, we report a new knee cartilage and bone segmentation framework, KCB-Net, for 3D MR images based on sparse annotation. KCB-Net selects a small subset of slices from 3D images for annotation, and seeks to bridge the performance gap between sparse annotation and full annotation. Specifically, it first identifies a subset of the most effective and representative slices with an unsupervised scheme; it then trains an ensemble model using the annotated slices; next, it self-trains the model using 3D images containing pseudo-labels generated by the ensemble method and improved by a bi-directional hierarchical earth mover's distance (bi-HEMD) algorithm; finally, it fine-tunes the segmentation results using the primal-dual Internal Point Method (IPM). Experiments on four 3D MR knee joint datasets (the SKI10 dataset, OAI ZIB dataset, Iowa dataset, and iMorphics dataset) show that our new framework outperforms state-of-the-art methods on full annotation, and yields high quality results for small annotation ratios even as low as 10%.


Pet ownership as a meaningful community occupation for people with serious mental illness.
We determined the proportion of pet owners and non-pet owners with serious mental illness, compared their characteristics and their motivations for owning or not owning a pet, and examined the relationship between pet ownership and engagement in meaningful activity and three dimensions of community integration. Three Assertive Community Treatment (ACT) teams reported on the pet ownership of all service recipients (N = 204). Of these recipients, 60 completed a survey. Nonparametric tests were selected for data analysis. Of 204 ACT clients, 38 (18.6%) were pet owners. Twenty-tour (63.2%) of 38 responding non-pet owners desired to live with a pet. There were significant differences between groups on diagnosis, gender, a global measure of function, meaningful activity, and psychological integration. The key finding supports the hypothesis that pet owners with serious mental illness living in the community demonstrate higher social community integration. Implications for future research and practice are discussed.


Effect of removable partial dentures on oral health-related quality of life in subjects with shortened dental arches: a 2-center cross-sectional study.
To assess the value of removable partial dentures (RPDs) in subjects with shortened dental arches (SDAs) with regard to quality of life. Subjects from 2 university dental centers (82 men, 78 women; mean age: 54 +/- 18 years) were categorized into the following groups: (1) SDA with intact anterior regions (SDA-1, n = 44); (2) SDA and interrupted anterior region (SDA-2, n = 21); (3) SDA (intact anterior region) extended with distal-extension RPD (RPD-1, n = 25); (4) subjects with interrupted SDA and interrupted anterior region treated with RPD (RPD-2, n = 32); or (5) complete dental arches (CDA, n = 38) as a control. All subjects underwent a short clinical examination and completed 2 structured questionnaires: the Oral Health Impact Profile (OHIP-49) and the Short-Form Health Survey (SF-36). Recorded clinical variables included: teeth present (yes/no), replacement by RPD (yes/no), and number of occlusal units. Age-dependent outcomes were adjusted to outcomes for the age of 60 years. Linear regression models were used to assess differences between the groups. Reliability and validity were good for all subscales. For OHIP, the investigation groups had significantly higher scores (more complaints) than CDA for the subscales "functional limitation," "psychologic discomfort," and "physical disability." Of the 4 investigation groups, SDA-1 subjects had the lowest mean scores. SF-36 scores showed less prominent and less conclusive differences between investigation groups and CDA subjects. SDA-2 subjects showed worse health, with significantly lower scores than RPD-2 subjects for "vitality," "social function," and "mental health." For pure SDA subjects (SDA-1) there was a significant positive effect for "number of occlusal units" in 5 of the OHIP subscales and 2 of the SF-36 subscales. From a quality-of-life perspective, patients with SDAs perceive benefits from RPDs only if anterior teeth replacements are included. In contrast, in subjects with uninterrupted SDAs, where only posterior teeth were replaced by distal-extension RPDs, such benefits could not be demonstrated.


Tropical Vegetable Oils Do Not Alter Growth Performance in African Catfish through a High n-6 Polyunsaturated Fatty Acids Biosynthesis Capacity.
The main objective of this study was to determine the best vegetable oils (VO) for nutrition of African catfish by assessing the effects of a complete replacement of fish oil (FO) by different VO sources on its growth performance, fatty acid composition, and elongase-desaturase gene expression levels. Fish (16.2 g of initial body weight) were fed with five experimental isonitrogenous, isolipidic, and isoenergetic diets in which FO was totally replaced by cottonseed oil (CO), palm oil (PO), desert date oil (DO), or Shea butter (SB). Complete replacement of FO with VO did not affect growth performance except for low values in fish fed SB diet. Muscle n-3 LC-polyunsaturated fatty acids (PUFA) were significantly reduced in fish fed VO-based diets when compared with FO fed fish. However, the muscle arachidinic acid (ARA) levels in phospholipid class were 1.4 to 1.6 times higher in fish fed CO and DO diets than FO fed fish despite the lower ARA suppliers from these VO-based diets, suggesting endogenous LC-PUFA biosynthesis from PUFA precursors in fish fed these VO. The fads2 and elovl5 gene expression levels in liver of fish fed DO were also higher compared to FO controls. Therefore, all the results support the hypothesis that African catfish has higher biosynthesis capacity to convert vegetable n-6 PUFA precursors like linoleic acid (LNA, 18:2n-6) into n-6 LC-PUFA of the ARA type, compared to the conversion of vegetable α-linolenic acid (ALA, 18:3n-3) into n-3 LC-PUFA of the eicosapentanoic acid (EPA) or docosahexanoic acid (DHA) type. The results also indicate that DO can be recommended as the best alternative to FO replacement in African catfish nutrition.


Differential LEF1 and TCF4 expression is involved in melanoma cell phenotype switching.
Recent observations suggest that melanoma cells drive disease progression by switching back and forth between phenotypic states of proliferation and invasion. Phenotype switching has been linked to changes in Wnt signalling, and we therefore looked for cell phenotype-specific differences in the levels and activity of β-catenin and its LEF/TCF co-factors. We found that while cytosolic β-catenin distribution is phenotype-specific (membrane-associated in proliferative cells and cytosolic in invasive cells), its nuclear distribution and activity is not. Instead, the expression patterns of two β-catenin co-factors, LEF1 and TCF4, are both phenotype-specific and inversely correlated. LEF1 is preferentially expressed by differentiated/proliferative phenotype cells and TCF4 by dedifferentiated/invasive phenotype cells. Knock-down experiments confirmed that these co-factors are important for the phenotype-specific expression of M-MITF, WNT5A and other genes and that LEF1 suppresses TCF4 expression independently of β-catenin. Our data show that melanoma cell phenotype switching behaviour is regulated by differential LEF1/TCF4 activity.


Development and Full Body Validation of a 5th Percentile Female Finite Element Model.
To mitigate the societal impact of vehicle crash, researchers are using a variety of tools, including finite element models (FEMs). As part of the Global Human Body Models Consortium (GHBMC) project, comprehensive medical image and anthropometrical data of the 5th percentile female (F05) were acquired for the explicit purpose of FEM development. The F05-O (occupant) FEM model consists of 981 parts, 2.6 million elements, 1.4 million nodes, and has a mass of 51.1 kg. The model was compared to experimental data in 10 validation cases ranging from localized rigid hub impacts to full body sled cases. In order to make direct comparisons to experimental data, which represent the mass of an average male, the model was compared to experimental corridors using two methods: 1) post-hoc scaling the outputs from the baseline F05-O model and 2) geometrically morphing the model to the body habitus of the average male to allow direct comparisons. This second step required running the morphed full body model in all 10 simulations for a total of 20 full body simulations presented. Overall, geometrically morphing the model was found to more closely match the target data with an average ISO score for the rigid impacts of 0.76 compared to 0.67 for the scaled responses. Based on these data, the morphed model was then used for model validation in the vehicle sled cases. Overall, the morphed model attained an average weighted score of 0.69 for the two sled impacts. Hard tissue injuries were also assessed and the baseline F05-O model was found to predict a greater occurrence of pelvic fractures compared to the GHBMC average male model, but predicted fewer rib fractures.


Lizards infected with malaria: physiological and behavioral consequences.
In northern California, western fence lizards, Sceloporus occidentalis, are frequently parasitized by Plasmodium mexicanum, which causes malaria. Animals with this naturally occurring malarial infection are anemic: immature erythrocytes in peripheral blood become abundant (1 to 30 percent), and blood hemoglobin concentration decreases 25 percent. Maximal oxygen consumption decreases 15 percent and aerobic scope drops 29 percent in infected lizards; both correlate with blood hemoglobin concentration. Running stamina, but not burst running speed, is reduced in malarious lizards. There is a hierarchical relation between infection with malaria and effects on hematology, physiological function, and behavioral capacity. The results suggest that malarial infection may have significant effects on the ecology of lizard hosts.


Electron emission from diamondoids: a diffusion quantum Monte Carlo study.
We present density-functional theory (DFT) and quantum Monte Carlo (QMC) calculations designed to resolve experimental and theoretical controversies over the optical properties of H-terminated C nanoparticles (diamondoids). The QMC results follow the trends of well-converged plane-wave DFT calculations for the size dependence of the optical gap, but they predict gaps that are 1-2 eV higher. They confirm that quantum confinement effects disappear in diamondoids larger than 1 nm, which have gaps below that of bulk diamond. Our QMC calculations predict a small exciton binding energy and a negative electron affinity (NEA) for diamondoids up to 1 nm, resulting from the delocalized nature of the lowest unoccupied molecular orbital. The NEA suggests a range of possible applications of diamondoids as low-voltage electron emitters.


A vacuum device for penile elongation: fact or fiction?
To assess the efficacy of a vacuum device as a noninvasive method for penile elongation. Between September 2003 and November 2004, 37 sexually active men with a stretched penis length of <10 cm were given vacuum treatment three times a week, for 20 min on each occasion, for 6 months. After 6 months, the mean penile length had increased from 7.6 cm to 7.9 cm (no significant difference). The efficacy of vacuum treatment was approximately 10%, and the patient satisfaction rate was 30%. There was one case of haematoma of the penis and one of glans numbness, both resolved spontaneously without any intervention. Vacuum treatment of the penis is not an effective method for penile elongation, but provides psychological satisfaction for some men.


Regulation of toxin synthesis in Clostridium difficile by an alternative RNA polymerase sigma factor.
Clostridium difficile, a causative agent of antibiotic-associated diarrhea and its potentially lethal form, pseudomembranous colitis, produces two large protein toxins that are responsible for the cellular damage associated with the disease. The level of toxin production appears to be critical for determining the severity of the disease, but the mechanism by which toxin synthesis is regulated is unknown. The product of a gene, txeR, that lies just upstream of the tox gene cluster was shown to be needed for tox gene expression in vivo and to activate promoter-specific transcription of the tox genes in vitro in conjunction with RNA polymerases from C. difficile, Bacillus subtilis, or Escherichia coli. TxeR was shown to function as an alternative sigma factor for RNA polymerase. Because homologs of TxeR regulate synthesis of toxins and a bacteriocin in other Clostridium species, TxeR appears to be a prototype for a novel mode of regulation of toxin genes.


Effects of Scarification, Phytohormones, Soil Type, and Warming on the Germination and/or Seedling Performance of Three Tamaulipan Thornscrub Forest Species.
The Tamaulipan thornforests of south Texas and northeast Mexico are an ecologically and economically important conservation hotspot. Thornforest restoration is limited by native tree and shrub seedling availability for planting. Seedling shortages arise from low seed availability and knowledge gaps regarding best practices for germinating and growing the 70+ thornforest species desired for restoration plantings. To fill key knowledge gaps, we investigated three ecologically important thornforest species with low or highly variable germination or seedling survival rates: Ebenopsis ebano, Cordia boissieri, and Zanthoxylum fagara. For each, we quantified the effects of different dosages of chemical seed treatments used to promote germination (sulfuric acid, SA; gibberellic acid, GA; indole-3-butyric acid, IBA) on germination likelihood and timing. We also quantified the effects that these chemical seed treatments, soil media mixture type, and soil warming had on seedling survival, growth, and root morphology. Ebenopsis germination peaked (>90%) with 40-60 min SA treatment. Cordia germination peaked (40%) with 100 mg/L GA treatment. Zanthoxylum germination was negligible across all treatments. Seed molding was rare but stirring during SA treatment reduced Ebenopsis molding by 4%. Ebenopsis seedling survival, height, leaf count, and root morphology were minimally affected by seed treatments, generally reduced by warming, and influenced by soil mix, which also mediated responses to warming. These results suggest improvements to existing practices that could increase Ebenopsis germination by 10-20% and potentially double Cordia germination.


AcK-knowledge reversible acetylation.
In 1966, the histone was identified as the first protein subject to reversible acetylation. The ensuing 30 years of research on histone acetylation has been critical for elucidating how gene transcription and chromatin remodeling are regulated at the molecular level. This central focus on histones, however, has also restricted our understanding of reversible acetylation, and therefore the enzymes that catalyze this reaction, to cellular processes predominantly associated with chromatin. The study of reversible acetylation has become more or less synonymous with histone acetylation. Recent developments-including increased ability to detect acetylated proteins, the characterization of novel acetyltransferases and deacetylases, and the identification of specific inhibitors for these enzymes-have revealed that this histone-central paradigm probably reflects only a fraction of the cellular processes regulated by reversible acetylation. New studies have uncovered unexpected roles for reversible acetylation in many diverse areas, thereby establishing protein acetylation as a highly versatile signaling modification that has functions beyond gene transcription and chromatin remodeling.


Generation of tumor antigen-specific T cell lines from pediatric patients with acute lymphoblastic leukemia--implications for immunotherapy.
Although modern cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 80%, the outlook remains poor in patients with high-risk disease and those who relapse, especially when allogeneic hematopoietic stem cell transplantation is not feasible. Strategies to improve outcome and prevent relapse are therefore required. Immunotherapy with antigen-specific T cells can have antileukemic activity without the toxicities seen with intensive chemotherapy, and therefore represents an attractive strategy to improve the outcome of high-risk patients with ALL. We explored the feasibility of generating tumor antigen-specific T cells ex vivo from the peripheral blood of 50 patients with ALL [26 National Cancer Institute (NCI) high-risk and 24 standard-risk] receiving maintenance therapy. Peripheral blood mononuclear cells were stimulated with autologous dendritic cells pulsed with complete peptide libraries of WT1, Survivin, MAGE-A3, and PRAME, antigens frequently expressed on ALL blasts. T-cell lines were successfully expanded from all patients, despite low lymphocyte counts and irrespective of NCI risk group. Antigen-specificity was observed in more than 50% of patients after the initial stimulation and increased to more than 90% after three stimulations as assessed in IFN-γ-enzyme-linked immunospot (ELISpot) and (51)Cr-release assays. Moreover, tumor-specific responses were observed by reduction of autologous leukemia blasts in short- and long-term coculture experiments. This study supports the use of immunotherapy with adoptively transferred autologous tumor antigen-specific T cells to prevent relapse and improve the prognosis of patients with high-risk ALL.


Longimicrobium terrae gen. nov., sp. nov., an oligotrophic bacterium of the under-represented phylum Gemmatimonadetes isolated through a system of miniaturized diffusion chambers.
A novel chemo-organoheterotroph bacterium, strain CB-286315T, was isolated from a Mediterranean forest soil sampled at the Sierra de Tejeda, Almijara and Alhama Natural Park, Spain, by using the diffusion sandwich system, a device with 384 miniature diffusion chambers. 16S rRNA gene sequence analyses identified the isolate as a member of the under-represented phylum Gemmatimonadetes, where 'Gemmatirosa kalamazoonensis' KBS708, Gemmatimonas aurantiaca T-27T and Gemmatimonas phototrophica AP64T were the closest relatives, with respective similarities of 84.4, 83.6 and 83.3 %. Strain CB-286315T was characterized as a Gram-negative, non-motile, short to long rod-shaped bacterium. Occasionally, some cells attained an unusual length, up to 35-40 μm. The strain showed positive responses for catalase and cytochrome-c oxidase and division by binary fission, and exhibited an aerobic metabolism, showing optimal growth under normal atmospheric conditions. Strain CB-286315T was also able to grow under micro-oxic atmospheres, but not under anoxic conditions. The strain is a slowly growing bacterium able to grow under low nutrient concentrations. Major fatty acids included iso-C17 : 1ω9c, summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH), C16 : 0 and iso-C17 : 0. The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two unidentified glycolipids and three phospholipids. The major isoprenoid quinone was MK-8 and the diagnostic diamino acid was meso-diaminopimelic acid. The DNA G+C content was 67.0 mol%. Based on a polyphasic taxonomic characterization, strain CB-286315T represents a novel genus and species, Longimicrobium terrae gen. nov., sp. nov., within the phylum Gemmatimonadetes. The type strain of Longimicrobium terrae is strain CB-286315T ( = DSM 29007T = CECT 8660T). In order to classify the novel taxon within the existing taxonomic framework, the family Longimicrobiaceae fam. nov., order Longimicrobiales ord. nov. and class Longimicrobia classis nov. are also proposed.


A study of physiological responses during match play in Indian national kabaddi players.
To determine the physical and physiological profile of kabaddi players and the physiological demands of playing a kabaddi match. Maximum aerobic capacity (VO2max), maximum ventilation (VEmax), O2 pulse, respiratory equivalent (RE), maximum heart rate, and O2 debt were assessed on 16 players. The somatotype of the players was calculated by the Health and Carter method. Heart rate was monitored during a selection trial match on eight players who represented India in the Asian Games, 1994. From the playing heart rate, oxygen consumption (VO2) was computed through a heart rate v VO2 regression equation. Maximum lactate was evaluated from the blood samples collected at the end of the match. The average heart rate and oxygen consumption during the match were 146.5 (SD 9.25) beats min-1 and 2.25(0.59) litre min-1 respectively. During raiding the maximum heart rate attained varied from 162.4(11.3) to 177.4(4.2) beats min-1. Out of 40 min of match play a raider raided on average on 8.13(2.03) occasions. The average time per raid was 20.8(6.26) s. The match heart rate and oxygen consumption was 72.3-83.3% of the maximum heart rate, and 43.5-70.5% of VO2max respectively. Maximum lactate at the end of the match was 6.13(2.53) mmol litre-1. Kabaddi players had the somatotype of 2.68-4.71-1.83, with absolute back strength of 175.0 kg. VO2max and O2 debt were 3.59(0.36) litre min-1 [47.82(3.68) ml kg-1 min-1] and 5.3(1.85) litres (70 ml kg-1) respectively. Kabaddi is an intermittent sport. The rest pause during the game is sufficient for recovery. During raiding the main source of energy is anaerobic.


Are effects of emotion in single words non-lexical? Evidence from event-related brain potentials.
Emotional meaning impacts word processing. However, it is unclear, at which functional locus this influence occurs and whether and how it depends on word class. These questions were addressed by recording event-related potentials (ERPs) in a lexical decision task with written adjectives, verbs, and nouns of positive, negative, and neutral emotional valence. In addition, word frequency (high vs. low) was manipulated. The early posterior negativity (EPN) in ERPs started earlier for emotional nouns and adjectives than for verbs. Depending on word class, EPN onsets coincided with or followed the lexicality effects. Main ERP effects of emotion overlapped with effects of word frequency between 300 and 550 ms but interacted with them only after 500 ms. These results indicate that in all three word classes examined, emotional evaluation as represented by the EPN has a post-lexical locus, starting already after a minimum of lexical access.


[Plasmapheresis and immunoglobulin therapy].
Plasmapheresis (PP) and intravenous immunoglobulin (IVIG) are both effective for treatment of crisis and acute exacerbation of myasthenia gravis. The 1(st) clinical problem is that effect of both treatments usually lasts for only 2-3 weeks. Additional immunosuppressive treatments may be necessary for prevention of the relapse. The 2(nd) problem is adverse effects and complications associated with each treatment. Hypotension, including shock, thromboembolism, and opportunistic infections are major adverse events of PP. Awareness of these complications and careful practice should be solutions. IVIG complicates less adverse effects than PP. The cost of each treatment, which is expensive particularly in IVIG use, may become the 3(rd) problem. It should be important to clarify the appropriate number of PP and the dose of IVIG to improve myasthenic crisis.


Characterization of the stress-inducing effects of homocysteine.
The mechanism by which homocysteine causes endothelial cell (EC) injury and/or dysfunction is not fully understood. To examine the stress-inducing effects of homocysteine on ECs, mRNA differential display and cDNA microarrays were used to evaluate changes in gene expression in cultured human umbilical-vein endothelial cells (HUVEC) exposed to homocysteine. Here we show that homocysteine increases the expression of GRP78 and GADD153, stress-response genes induced by agents or conditions that adversely affect the function of the endoplasmic reticulum (ER). Induction of GRP78 was specific for homocysteine because other thiol-containing amino acids, heat shock or H2O2 did not appreciably increase GRP78 mRNA levels. Homocysteine failed to elicit an oxidative stress response in HUVEC because it had no effect on the expression of heat shock proteins (HSPs) including HSP70, nor did it activate heat shock transcription factor 1. Furthermore homocysteine blocked the H2O2-induced expression of HSP70. In support of our findings in vitro, steady-state mRNA levels of GRP78, but not HSP70, were elevated in the livers of cystathionine beta-synthase-deficient mice with hyperhomocysteinaemia. These studies indicate that the activation of stress response genes by homocysteine involves reductive stress leading to altered ER function and is in contrast with that of most other EC perturbants. The observation that homocysteine also decreases the expression of the antioxidant enzymes glutathione peroxidase and natural killer-enhancing factor B suggests that homocysteine could potentially enhance the cytotoxic effect of agents or conditions known to cause oxidative stress.


Enzyme molecules in solitary confinement.
Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.


Role of EP(2) and EP(3) PGE(2) receptors in control of murine renal hemodynamics.
The kidney plays a central role in long-term regulation of arterial blood pressure and salt and water homeostasis. This is achieved in part by the local actions of paracrine and autacoid mediators such as the arachidonic acid-prostanoid system. The present study tested the role of specific PGE(2) E-prostanoid (EP) receptors in the regulation of renal hemodynamics and vascular reactivity to PGE(2). Specifically, we determined the extent to which the EP(2) and EP(3) receptor subtypes mediate the actions of PGE(2) on renal vascular tone. Renal blood flow (RBF) was measured by ultrasonic flowmetry, whereas vasoactive agents were injected directly into the renal artery of male mice. Studies were performed on two independent mouse lines lacking either EP(2) or EP(3) (-/-) receptors and the results were compared with wild-type controls (+/+). Our results do not support a unique role of the EP(2) receptor in regulating overall renal hemodynamics. Baseline renal hemodynamics in EP(2)-/- mice [RBF EP(2)-/-: 5.3 +/- 0.8 ml. min(-1). 100 g kidney wt(-1); renal vascular resistance (RVR) 19.7 +/- 3.6 mmHg. ml(-1). min. g kidney wt] did not differ statistically from control mice (RBF +/+: 4.0 +/- 0.5 ml. min(-1). 100 g kidney wt(-1); RVR +/+: 25.4 +/- 4.9 mmHg. ml(-1). min. 100 g kidney wt(-1)). This was also the case for the peak RBF increase after local PGE(2) (500 ng) injection into the renal artery (EP(2)-/-: 116 +/- 4 vs. +/+: 112 +/- 2% baseline RBF). In contrast, we found that the absence of EP(3) receptors in EP(3)-/- mice caused a significant increase (43%) in basal RBF (7.9 +/- 0.8 ml. min(-1). g kidney wt(-1), P < 0.05 vs. +/+) and a significant decrease (41%) in resting RVR (11.6 +/- 1.4 mmHg. ml(-1). min. g kidney wt(-1), P < 0.05 vs. +/+). Local administration of 500 ng of PGE(2) into the renal artery caused more pronounced renal vasodilation in EP(3)-/- mice (128 +/- 2% of basal RBF, P < 0.05 vs. +/+). We conclude that EP(3 )receptors mediate vasoconstriction in the kidney of male mice and its actions are tonically active in the basal state. Furthermore, EP(3) receptors are capable of buffering PGE(2)-mediated renal vasodilation.


Manipulation of Human Primary Endothelial Cell and Osteoblast Coculture Ratios to Augment Vasculogenesis and Mineralization.
Tissue-engineering scaffolds are often seeded with a single type of cell, but there has been more focus on cocultures to improve angiogenesis and bone formation for craniofacial applications. Investigation of bone-derived osteoblasts (OBs) is important because of the use of bone grafts and migration of OBs from native bone into constructs in vivo and therefore, their contribution to bone formation in vivo. The limitation of primary OBs has been their inability to mineralize without osteogenic factors in vitro. Through coculture of OBs and endothelial cells (ECs) and manipulation of the coculture ratio, mineralization can be achieved without osteogenic media or additional growth factors, thus enhancing their utility for tissue-engineering applications. An optimal ratio of EC/OB for vasculogenesis and mineralization has not been determined for human primary cells. Human umbilical vein ECs were cultured with normal human primary OBs in different EC/OB ratios, namely, 10:1, 5:1, 1:1, 1:5, and 1:10 with EC and OB monocultures as controls. The number of vasculogenic networks in a collagen matrix was highest in ratios of 5:1 and 1:1. ECs lined up and formed capillary-like networks by day 10, which was not seen in the other groups. On polystyrene, cells were cocultured with ECs and OBs in direct contact (direct coculture) or separated by a transwell membrane (indirect coculture). At day 21, Alizarin Red staining showed mineralization on the 1:5 and 1:10 direct coculture ratios, with 1:5 having more mineralization nodules present than 1:10. No mineralization was seen in other direct coculture ratios or in any of the indirect coculture ratios. Alkaline phosphatase secretion was highest in the 1:5 direct coculture group. Vascular endothelial growth factor secretion from OBs was present in the 1:5 and 1:10 direct coculture ratios at all time points and inhibited after day 1 in other coculture groups. To improve vasculogenesis, cocultures of primary human ECs and OBs in ratios of 5:1 should be used, but to improve bone formation, the 1:5 direct coculture ratio results in most mineralization.


Efficacy of adhesion barriers. Resorbable hydrogel, oxidized regenerated cellulose and hyaluronic acid.
To compare a novel resorbable hydrogel barrier with two previously studied barriers, oxidized regenerated cellulose and hyaluronic acid, for the prevention of postoperative adhesions. Two models were employed in the rat uterine horn, one of adhesion formation after devascularization and serosal injury and one of adhesion reformation after adhesiolysis In the devascularization model, hydrogel treatment reduced the mean extent of adhesion formation from 73% in the control group to 13% (P < .005). Hyaluronic acid pretreatment reduced the extent of adhesion formation to 44% (P < .05), while oxidized regenerated cellulose failed to reduce formation (P > .25). In the adhesiolysis model, treatment with the hydrogel reduced the mean extent of adhesion formation from 87% in the control group to 20% (P < .005). Neither the oxidized regenerated cellulose nor the hyaluronic acid treatments lowered the extent of adhesion formation from the control group (P > .25). The hydrogel barrier was observed to be resorbed over a five-day period and remained adherent to the tissue during resorption. Resorbable hydrogel barriers are highly effective in the reduction of adhesion formation and reformation in the rat. This probably due to the good biocompatibility and retention of these materials upon the site of application.


Impacts of ionising radiation on sperm quality, DNA integrity and post-fertilisation development in marine and freshwater crustaceans.
Crustaceans have been designated as internationally important model organisms in the development of environmental radioprotection measures. Despite the known sensitivity of sperm to ionizing radiation, the impacts of chronic radiation exposure on male fertility in crustaceans have not been studied. For the first time, the present study aimed to assess the impacts of chronic radiation exposure on male fertility, sperm DNA damage and concomitant impacts on breeding in two amphipod crustaceans. Echinogammarus marinus and Gammarus pulex (male fertility only) were exposed to phosphorus-32 at dose rates of 0, 0.1, 1 and 10 mGy/d and sperm parameters, DNA damage and knock-on impacts on breeding were assessed. Sperm quality parameters and DNA damage were assessed using a fluorescent staining method and single cell gel electrophoresis respectively. Concomitant effects of male exposure to radiation on fecundity were determined by pairing phosphorus-32 exposed males to unexposed sexually mature females. In E. marinus, a statistically significant reduction of 9 and 11% in the quality of sperm was recorded at dose rates of 1 and 10 mGy/d respectively, with no significant effects recorded on sperm counts. Conversely in the freshwater G. pulex, no significant impact of radiation on sperm quantity or quality was recorded. For E. marinus, a statistically significant increase in DNA damage was recorded at doses of 10 mGy/d. Reduced fecundity and an increase in the frequency of abnormal embryos was recorded in female E. marinus breeding with males exposed to radiation. These findings suggest sperm quality may be a sensitive indicator of radiation exposure in invertebrates with potential impacts on the unexposed embryo, though unclear dose-response and differences between two closely related species necessitate further study before robust conclusions can be drawn.


Factors associated with supermarket and convenience store closure: a discrete time spatial survival modelling approach.
While there is a literature on the distribution of food stores across geographic and social space, much of this research uses cross-sectional data. Analyses attempting to understand whether the availability of stores across neighborhoods is associated with diet and/or health outcomes are limited by a lack of understanding of factors that shape the emergence of new stores and the closure of others. We used quarterly data on supermarket and convenience store locations spanning seven years (2006-2012) and tract-level census data in four US cities: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; San Francisco, California. A spatial discrete-time survival model was used to identify factors associated with an earlier and/or later closure time of a store. Sales volume was typically the strongest indicator of store survival. We identified heterogeneity in the association between tract-level poverty and racial composition with respect to store survival. Stores in high poverty, non-White tracts were often at a disadvantage in terms of survival length. The observed patterns of store survival varied by some of the same neighborhood sociodemographic factors associated with lifestyle and health outcomes, which could lead to confusion in interpretation in studies of the estimated effects of introduction of food stores into neighborhoods on health.


A PEGylation-Free Biomimetic Porphyrin Nanoplatform for Personalized Cancer Theranostics.
PEGylation (PEG) is the most commonly adopted strategy to prolong nanoparticles' vascular circulation by mitigating the reticuloendothelial system uptake. However, there remain many concerns in regards to its immunogenicity, targeting efficiency, etc., which inspires pursuit of alternate, non-PEGylated systems. We introduced here a PEG-free, porphyrin-based ultrasmall nanostructure mimicking nature lipoproteins, termed PLP, that integrates multiple imaging and therapeutic functionalities, including positron emission tomography (PET) imaging, near-infrared (NIR) fluorescence imaging and photodynamic therapy (PDT). With an engineered lipoprotein-mimicking structure, PLP is highly stable in the blood circulation, resulting in favorable pharmacokinetics and biodistribution without the need of PEG. The prompt tumor intracellular trafficking of PLP allows for rapid nanostructure dissociation upon tumor accumulation to release monomeric porphyrins to efficiently generate fluorescence and photodynamic reactivity, which are highly silenced in intact PLP, thus providing an activatable mechanism for low-background NIR fluorescence imaging and tumor-selective PDT. Its intrinsic copper-64 labeling feature allows for noninvasive PET imaging of PLP delivery and quantitative assessment of drug distribution. Using a clinically relevant glioblastoma multiforme model, we demonstrated that PLP enabled accurate delineation of tumor from surrounding healthy brain at size less than 1 mm, exhibiting the potential for intraoperative fluorescence-guided surgery and tumor-selective PDT. Furthermore, we demonstrated the general applicability of PLP for sensitive and accurate detection of primary and metastatic tumors in other clinically relevant animal models. Therefore, PLP offers a biomimetic theranostic nanoplatform for pretreatment stratification using PET and NIR fluorescence imaging and for further customized cancer management via imaging-guided surgery, PDT, or/and potential chemotherapy.


Interaction between ROCK II and nucleophosmin/B23 in the regulation of centrosome duplication.
Nucleophosmin (NPM)/B23 has been implicated in the regulation of centrosome duplication. NPM/B23 localizes between two centrioles in the unduplicated centrosome. Upon phosphorylation on Thr(199) by cyclin-dependent kinase 2 (CDK2)/cyclin E, the majority of centrosomal NPM/B23 dissociates from centrosomes, but some NPM/B23 phosphorylated on Thr(199) remains at centrosomes. It has been shown that Thr(199) phosphorylation of NPM/B23 is critical for the physical separation of the paired centrioles, an initial event of the centrosome duplication process. Here, we identified ROCK II kinase, an effector of Rho small GTPase, as a protein that localizes to centrosomes and physically interacts with NPM/B23. Expression of the constitutively active form of ROCK II promotes centrosome duplication, while down-regulation of ROCK II expression results in the suppression of centrosome duplication, especially delaying the initiation of centrosome duplication during the cell cycle. Moreover, ROCK II regulates centrosome duplication in its kinase and centrosome localization activity-dependent manner. We further found that ROCK II kinase activity is significantly enhanced by binding to NPM/B23 and that NPM/B23 acquires a higher binding affinity to ROCK II upon phosphorylation on Thr(199). Moreover, physical interaction between ROCK II and NPM/B23 in vivo occurs in association with CDK2/cyclin E activation and the emergence of Thr(199)-phosphorylated NPM/B23. All these findings point to ROCK II as the effector of the CDK2/cyclin E-NPM/B23 pathway in the regulation of centrosome duplication.


Group II metabotropic glutamate receptors depress synaptic transmission onto subicular burst firing neurons.
The subiculum (SUB) is a pivotal structure positioned between the hippocampus proper and various cortical and subcortical areas. Despite the growing body of anatomical and intrinsic electrophysiological data of subicular neurons, modulation of synaptic transmission in the SUB is not well understood. In the present study we investigated the role of group II metabotropic glutamate receptors (mGluRs), which have been shown to be involved in the regulation of synaptic transmission by suppressing presynaptic cAMP activity. Using field potential and patch-clamp whole cell recordings we demonstrate that glutamatergic transmission at CA1-SUB synapses is depressed by group II mGluRs in a cell-type specific manner. Application of the group II mGluR agonist (2S,1'R,2'R,3'R)-2-(2, 3-dicarboxycyclopropyl)glycine (DCG-IV) led to a significantly higher reduction of excitatory postsynaptic currents in subicular bursting cells than in regular firing cells. We further used low-frequency stimulation protocols and brief high-frequency bursts to test whether synaptically released glutamate is capable of activating presynaptic mGluRs. However, neither frequency facilitation is enhanced in the presence of the group II mGluR antagonist LY341495, nor is a test stimulus given after a high-frequency burst. In summary, we present pharmacological evidence for presynaptic group II mGluRs targeting subicular bursting cells, but both low- and high-frequency stimulation protocols failed to activate presynaptically located mGluRs.


PREVALENCE AND MOLECULAR CHARACTERIZATION OF DIROFILARIA IMMITIS (FILARIOIDEA: ONCHOCERCIDAE) IN DOGS FROM ENDEMIC AREAS OF RIO DE JANEIRO STATE, BRAZIL.
Canine dirofilariasis is common in Brazil, but molecular diagnosis is rare even though molecular studies increase our knowledge about molecular epidemiology and circulating genotypes from helminths worldwide. This study aims to estimate the prevalence of infection with a modified Knott's test and to perform molecular characterization of Dirofilaria immitis (Leidy, 1856) Railliet and Henry, 1911, in dogs from endemic areas of Maricá and Niterói municipalities, Rio de Janeiro State, Brazil. Molecular characterization was performed in 33 blood samples from dogs positive for microfilariae and 4 adult worms obtained from 2 other dogs. DNA extraction followed by PCR for mitochondrial target 12S rDNA and cytochrome oxidase subunit 1 (COI) of D. immitis were performed, and the amplified products were sequenced. All sequences were identical for both gene targets and showed 100% identity with D. immitis sequences from different animal species from various countries. The study concluded that this genotype of D. immitis might be dispersed worldwide.