The national public health performance standards: driving quality improvement in public health systems.
Since its inception in 1998, the Centers for Disease Control and Prevention's National Public Health Performance Standards Program (NPHPSP) has helped lay the groundwork for public health quality improvement (QI) activities at the state and local levels. This article describes how the NPHPSP has promoted QI through its instruments and guidance and how it has continually strengthened the focus on QI over the years. The NPHPSP Version 2 instruments and enhanced guidance have been designed to more strongly reinforce QI and catalyze the transition from assessment to action. Despite positive reports from some state and local users that emphasize the value the NPHPSP holds for those that do successfully move forward with improvement actions, 2005 evaluation results from the Association of State and Territorial Health Officials and the National Association of County and City Health Officials indicated challenges in transitioning the assessments results into performance improvement. More recent data are promising; a 2009 postassessment survey of early Version 2 respondents indicates that the majority (75% of all respondents) report action in one or more performance improvement steps. The NPHPSP has played an important role in fostering QI in many states and local jurisdictions. Furthermore, its experiences and lessons learned in supporting QI have helped to pave the way for other initiatives, such as the emerging national accreditation system for state and local health departments.


Population genomics of the Anthropocene: urbanization is negatively associated with genome-wide variation in white-footed mouse populations.
Urbanization results in pervasive habitat fragmentation and reduces standing genetic variation through bottlenecks and drift. Loss of genomewide variation may ultimately reduce the evolutionary potential of animal populations experiencing rapidly changing conditions. In this study, we examined genomewide variation among 23 white-footed mouse (Peromyscus leucopus) populations sampled along an urbanization gradient in the New York City metropolitan area. Genomewide variation was estimated as a proxy for evolutionary potential using more than 10 000 single nucleotide polymorphism (SNP) markers generated by ddRAD-Seq. We found that genomewide variation is inversely related to urbanization as measured by percent impervious surface cover, and to a lesser extent, human population density. We also report that urbanization results in enhanced genomewide differentiation between populations in cities. There was no pattern of isolation by distance among these populations, but an isolation by resistance model based on impervious surface significantly explained patterns of genetic differentiation. Isolation by environment modeling also indicated that urban populations deviate much more strongly from global allele frequencies than suburban or rural populations. This study is the first to examine loss of genomewide SNP variation along an urban-to-rural gradient and quantify urbanization as a driver of population genomic patterns.


What makes a face photo a 'good likeness'?
Photographs of people are commonly said to be 'good likenesses' or 'poor likenesses', and this is a concept that we readily understand. Despite this, there has been no systematic investigation of what makes an image a good likeness, or of which cognitive processes are involved in making such a judgement. In three experiments, we investigate likeness judgements for different types of images: natural images of film stars (Experiment 1), images of film stars from specific films (Experiment 2), and iconic images and face averages (Experiment 3). In all three experiments, participants rated images for likeness and completed speeded name verification tasks. We consistently show that participants are faster to identify images which they have previously rated asa good likeness compared to a poor likeness. We also consistently show that the more familiar we are with someone, the higher likeness rating we give to all images of them. A key finding is that our perception of likeness is idiosyncratic (Experiments 1 and 2), and can be tied to our specific experience of each individual (Experiment 2). We argue that likeness judgements require a comparison between the stimulus and our own representation of the person, and that this representation differs according to our prior experience with that individual. This has theoretical implications for our understanding of how we represent familiar people, and practical implications for how we go about selecting images for identity purposes such as photo-ID.


The use of the dual-task paradigm in detecting gait performance deficits following a sports-related concussion: a systematic review and meta-analysis.
The purpose of this systematic review was to determine the viability of the dual-task paradigm in the evaluation of a sports-related concussion. Systematic review and meta-analysis. Eight electronic databases were searched from their inception until the 11(th) of April 2011. Studies were grouped according to their reported gait performance variables and their time(s) of assessment(s). Raw mean differences (MD) and 95% confidence intervals (CI) were calculated based on raw means and standard deviations for gait performance measures in both single- and dual-task conditions. Dual-task deficits were pooled using a random effects model and heterogeneity (I(2)) between studies was assessed. Ten studies representing a total sample of 168 concussed and 167 matched (age and gender) non-concussed participants met the inclusion criteria. Meta-analysis demonstrated that dual-task performance deficits were detected (p<0.05) in the concussed group for gait velocity (GV) (MD=-0.133; 95% CI -0.197, -0.069) and range of motion of the centre of mass in the coronal plane (ML-ROM) (MD=0.007; 95% CI 0.002, 0.011), but not in the non-concussed group; GV (MD=-0.048; 95% CI -0.101, 0.006), ML-ROM (MD=0.002; 95% CI -0.001, 0.005). The results of this study indicate that GV and ML-ROM are sensitive measures of dual-task related changes in concussed patients and should be considered as part of a comprehensive assessment for a sports-related concussion.


Dopamine receptor repertoire of human granulosa cells.
High levels of dopamine (DA) were described in human ovary and recently evidence for DA receptors in granulosa and luteal cells has been provided, as well. However, neither the full repertoire of ovarian receptors for DA, nor their specific role, is established. Human granulosa cells (GCs) derived from women undergoing in vitro fertilization (IVF) are an adequate model for endocrine cells of the follicle and the corpus luteum and were therefore employed in an attempt to decipher their DA receptor repertoire and functionality. Cells were obtained from patients undergoing IVF and examined using cDNA-array, RT-PCR, Western blotting and immunocytochemistry. In addition, calcium measurements (with FLUO-4) were employed. Expression of two DA receptors was also examined by in-situ hybridization in rat ovary. Effects of DA on cell viability and cell volume were studied by using an ATP assay and an electronic cell counter system. We found members of the two DA receptor families (D1- and D2 -like) associated with different signaling pathways in human GCs, namely D1 (as expected) and D5 (both are Gs coupled and linked to cAMP increase) and D2, D4 (Gi/Gq coupled and linked to IP3/DAG). D3 was not found. The presence of the trophic hormone hCG (10 IU/ml) in the culture medium for several days did not alter mRNA (semiquantitative RT-PCR) or protein levels (immunocytochemistry/Western blotting) of D1,2,4,5 DA receptors. Expression of prototype receptors for the two families, D1 and D2, was furthermore shown in rat granulosa and luteal cells by in situ hybridization. Among the DA receptors found in human GCs, D2 expression was marked both at mRNA and protein levels and it was therefore further studied. Results of additional RT-PCR and Western blots showed two splice variants (D2L, D2S). Irrespective of these variants, D2 proved to be functional, as DA raised intracellular calcium levels. This calcium mobilizing effect of DA was observed in the absence of extracellular calcium and was abolished by a D2 blocker (L-741,626). DA treatment (48 h) of human GCs resulted in slightly, but significantly enlarged, viable cells. A previous study showed D2 in human GCs, which are linked to cAMP, and the present study reveals the full spectrum of DA receptors present in these endocrine cells, which also includes D2-like receptors, linked to calcium. Ovarian DA can act thus via D1,2,4,5, which are co-expressed by endocrine cells of the follicle and the corpus luteum and are linked to different signaling pathways. This suggests a complex role of DA in the regulation of ovarian processes.


A model for assessment of telemedicine applications: mast.
Telemedicine applications could potentially solve many of the challenges faced by the healthcare sectors in Europe. However, a framework for assessment of these technologies is need by decision makers to assist them in choosing the most efficient and cost-effective technologies. Therefore in 2009 the European Commission initiated the development of a framework for assessing telemedicine applications, based on the users' need for information for decision making. This article presents the Model for ASsessment of Telemedicine applications (MAST) developed in this study. MAST was developed through workshops with users and stakeholders of telemedicine. Based on the workshops and using the EUnetHTA Core HTA Model as a starting point a three-element model was developed, including: (i) preceding considerations, (ii) multidisciplinary assessment, and (iii) transferability assessment. In the multidisciplinary assessment, the outcomes of telemedicine applications comprise seven domains, based on the domains in the EUnetHTA model. MAST provides a structure for future assessment of telemedicine applications. MAST will be tested during 2010-13 in twenty studies of telemedicine applications in nine European countries in the EC project Renewing Health.


Bone reaction to a biomimetic third-generation hydroxyapatite coating and new surface treatment for the Symax hip stem.
Four uncemented Symax hip stems were extracted at three weeks and nine, 13 and 32 months, respectively, for reasons other than loosening. The reasons for implant removal were infection in two cases, recurrent dislocation in one and acetabular fracture in one. They were analysed to assess the effect and behaviour of an electrochemically deposited, completely resorbable biomimetic BONIT-hydroxyapatite (HA) coating (proximal part) and a DOTIZE surface treatment (distal part) using qualitative histology, quantitative histomorphometry and scanning electron microscopy (SEM). Early and direct bone-implant bonding with signs of active remodelling of bone and the HA coating were demonstrated by histology and SEM. No loose BONIT-HA particles or delamination of the coating were observed, and there was no inflammation or fibrous interposition at the interface. Histomorphometry showed bone-implant contact varying between 26.5% at three weeks and 83.5% at 13 months at the HA-coated implant surface. The bone density in the area of investigation was between 24.6% at three weeks and 41.1% at 32 months. The DOTIZE surface treatment of the distal part of the stem completely prevented tissue and bone apposition in all cases, thereby optimising proximal stress transfer. The overall features of this implant, in terms of geometry and surface texture, suggest a mechanically stable design with a highly active biomimetic coating, resulting in rapid and extensive osseo-integration, exclusively in the metaphyseal part of the stem. Early remodelling of the HA coating does not seem to have a detrimental effect on short-term bone-implant coupling. There were no adverse effects identified from either the BONIT-HA coating or the DOTIZE surface treatment.


Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease.
Kidney cysts occur following inactivation of polycystins in otherwise intact cilia or following complete removal of cilia by inactivation of intraflagellar transport-related proteins. We investigated the mechanisms of cyst formation in these two distinct processes by combining conditional inactivation of polycystins with concomitant ablation of cilia in developing and adult kidney and liver. We found that loss of intact cilia suppressed cyst growth following inactivation of polycystins and that the severity of cystic disease was directly related to the length of time between the initial loss of the polycystin proteins and the subsequent involution of cilia. This cilia-dependent cyst growth was not explained by activation of the MAPK/ERK, mTOR or cAMP pathways and is likely to be distinct from the mechanism of cyst growth following complete loss of cilia. These data establish the existence of a new pathway defined by polycystin-dependent inhibition and cilia-dependent activation that promotes rapid cyst growth.


Respiratory sinus arrhythmia in the denervated human heart.
We performed this study to test whether the denervated human heart has the ability to manifest respiratory sinus arrhythmia (RSA). With the use of a highly sensitive spectral analysis technique (cross correlation) to define beat-to-beat coupling between respiratory frequency and heart rate period (R-R) and hence RSA, we compared the effects of patterned breathing at defined respiratory frequency and tidal volumes (VT), Valsalva and Mueller maneuvers, single deep breaths, and unpatterned spontaneous breathing on RSA in 12 normal volunteers and 8 cardiac allograft transplant recipients. In normal subjects R-R changes closely followed changes in respiratory frequency (P less than 0.001) but were little affected by changes in VT. On the R-R spectrum, an oscillation peak synchronous with respiration was found in heart transplant patients. However, the average magnitude of the respiration-related oscillations was 1.7-7.9% that seen in normal subjects and was proportionally more influenced by changes in VT. Changes in R-R induced by Valsalva and Mueller maneuvers were 3.8 and 4.9% of those seen in normal subjects, respectively, whereas changes in R-R induced by single deep breaths were 14.3% of those seen in normal subjects. The magnitude of RSA was not related to time since the heart transplantation, neither was it related to patient age or sex. Thus the heart has the intrinsic ability to vary heart rate in synchrony with ventilation, consistent with the hypothesis that changes, or rate of changes, in myocardial wall stretch might alter intrinsic heart rate independent of autonomic tone.


Evolving Spiking Neural Networks for online learning over drifting data streams.
Nowadays huge volumes of data are produced in the form of fast streams, which are further affected by non-stationary phenomena. The resulting lack of stationarity in the distribution of the produced data calls for efficient and scalable algorithms for online analysis capable of adapting to such changes (concept drift). The online learning field has lately turned its focus on this challenging scenario, by designing incremental learning algorithms that avoid becoming obsolete after a concept drift occurs. Despite the noted activity in the literature, a need for new efficient and scalable algorithms that adapt to the drift still prevails as a research topic deserving further effort. Surprisingly, Spiking Neural Networks, one of the major exponents of the third generation of artificial neural networks, have not been thoroughly studied as an online learning approach, even though they are naturally suited to easily and quickly adapting to changing environments. This work covers this research gap by adapting Spiking Neural Networks to meet the processing requirements that online learning scenarios impose. In particular the work focuses on limiting the size of the neuron repository and making the most of this limited size by resorting to data reduction techniques. Experiments with synthetic and real data sets are discussed, leading to the empirically validated assertion that, by virtue of a tailored exploitation of the neuron repository, Spiking Neural Networks adapt better to drifts, obtaining higher accuracy scores than naive versions of Spiking Neural Networks for online learning environments.


Discriminant effects of behaviorally active and inactive analogs of phencyclidine on membrane electrical excitability.
The discriminant effects of several behaviorally active and inactive analogs of phencyclidine [PCP; 1-(phenylcyclohexyl) piperidine] and the actions of PCP and three Ca-channel antagonists were examined on electrical excitability in frog and crayfish skeletal muscles. In frog sartorius muscle, 1-[1-(2-thienylcyclohexyl)piperidine (TCP; 100 microM), a behaviorally active analog of PCP, increased action potential duration nearly 9-fold, blocked delayed rectification and at 0.5 to 1 microM also increased the quantal release of transmitter. A partial blockade of delayed rectification and slight prolongation of the action potential occurred with 1-(p-fluorophenylcyclohexyl)piperidine (p-F-PCP; 100 microM), which possesses about 25% of the behavioral activity of PCP. Of the remaining p-phenyl- substituted analogs which never exhibited more than 10% of the behavioral potency of PCP, only 1-(1-p-nitrophenylcyclohexyl)piperidine (p-NO2-PCP; 100 microM) produced a frequency-dependent prolongation of the action potential but, like the p-methoxy-, p-chloro- and p-methyl- analog, it did not block delayed rectification. The order of potencies of these analogs in blocking delayed rectification, prolonging the muscle action potential and in affecting alternation impairment and response rate depression is therefore: PCP much greater than TCP greater than p-F-PCP much greater than p-CH3-PCP = p-CH3O-PCP = p-Cl-PCP = p-NO2-PCP. Like PCP and its behaviorally active analogs, verapamil (50 microM) and bepridil (50 microM), two Ca-channel blockers, also blocked delayed rectification in frog sartorius muscles whereas nifedipine (50 microM), another Ca-channel blocker, did not.(ABSTRACT TRUNCATED AT 250 WORDS)


Conformational changes in thrombin when complexed by serpins.
Thrombin possesses two positively charged surface domains, termed exosites, that orient substrates and inhibitors for reaction with the enzyme. Because the exosites also allosterically modulate thrombin's activity, we set out to determine whether the structure or function of the exosites changes when thrombin forms complexes with antithrombin, heparin cofactor II, or alpha(1)-antitrypsin (M358R), serpins that utilize both, one, or neither of the exosites, respectively. Using a hirudin-derived peptide to probe the integrity of exosite 1, no binding was detected when thrombin was complexed with heparin cofactor II or alpha(1)-antitrypsin (M358R), and the peptide exhibited a 55-fold lower affinity for the thrombin-antithrombin complex than for thrombin. Bound peptide or HD-1, an exosite 1-binding DNA aptamer, was displaced from thrombin by each of the three serpins. Thrombin binding to fibrin also was abrogated when the enzyme was complexed with serpins. These data reveal that, regardless of the initial mode of interaction, the function of exosite 1 is lost when thrombin is complexed by serpins. In contrast, the integrity of exosite 2 is largely retained when thrombin is complexed by serpins, because interaction with heparin or an exosite 2-directed DNA aptamer was only modestly altered. The disorganization of exosite 1 that occurs when thrombin is complexed by serpins is consistent with results of protease sensitivity studies and crystallographic analysis of a homologous enzyme-serpin complex.


Salmonella population rebound and its prevention on spray washed and non-washed jalapeño peppers and roma tomatoes in humid storage.
The potential of Salmonella population to rebound on non-washed and washed roma tomatoes and jalapeño peppers in humid storage at 4°C, 10°C, 15°C, 21°C, or 35°C for ≤12 days was investigated. The initial inoculation levels of Salmonella on peppers and tomatoes were 5.6 and 5.2 log CFU/cm(2), respectively. Air-drying of fruit surfaces resulted in contamination levels of 3.9 and 3.7 log CFU/cm(2) on inoculated peppers and tomatoes, respectively. At 21°C and 35°C, the levels of air-dried Salmonella inoculums on produce surfaces increased ≥2 log cycles, with the most rapid growth in the first 3 days. Mechanical washing on rollers (rinsing; R-treatment) or revolving brushes (rinsing and brushing; RB-treatment) with water decreased Salmonella counts by ≥2.5 log CFU/cm(2) on both peppers and tomatoes. After R- or RB-treatment, peppers stored at 21°C and 35°C permitted residual Salmonella (≤1.4 log CFU/cm(2)) to grow to 2.6-3.9 log CFU/cm(2). During storage, residual Salmonella (≤1.0 log CFU/cm(2)) on washed tomatoes increased to 3.1 log CFU/cm(2) at 35°C following R-treatment and 3.8 log CFU/cm(2) at 21°C following RB-treatment. Cold storage at 4°C and 10°C effectively prevented the proliferation of Salmonella on both washed and non-washed produce. The current study on jalapeño peppers and roma tomatoes demonstrated that Salmonella population can rebound on produce in humid storage before or after washing. The finding highlights the benefit of uninterrupted cold storage for safer produce operations.


Molecular diagnosis of bird-mediated pest consumption in tropical farmland.
Biodiversity loss will likely have surprising and dramatic consequences for human wellbeing. Identifying species that benefit society represents a critical first step towards predicting the consequences of biodiversity loss. Though natural predators prevent billions of dollars in agricultural pest damage annually, characterizing which predators consume pests has proven challenging. Emerging molecular techniques may illuminate these interactions. In the countryside of Costa Rica, we identified avian predators of coffee's most damaging insect pest, the coffee berry borer beetle (Coleoptera:Scolytidae Hypothenemus hampeii), by assaying 1430 fecal samples of 108 bird species for borer DNA. While feeding trials confirmed the efficacy of our approach, detection rates were low. Nevertheless, we identified six species that consume the borer. These species had narrow diet breadths, thin bills, and short wings; traits shared with borer predators in other systems. Borer predators were not threatened; therefore, safeguarding pest control necessitates managing species beyond those at risk of regional extinction by maintaining populations in farmland habitats. Generally, our results demonstrate potential for pairing molecular methods with ecological analyses to yield novel insights into species interactions.


Computational modeling of oscillating fins that "catch and release" targeted nanoparticles in bilayer flows.
A number of physiological processes in living organisms involve the selective "catch and release" of biomolecules. Inspired by these biological processes, we use computational modeling to design synthetic systems that can controllably catch, transport, and release specific molecules within the surrounding solution, and, thus, could be harnessed for effective separation processes within microfluidic devices. Our system consists of an array of oscillating, microscopic fins that are anchored onto the floor of a microchannel and immersed in a flowing bilayer fluid. The oscillations drive the fins to repeatedly extend into the upper fluid and then tilt into the lower stream. The fins exhibit a specified wetting interaction with the fluids and specific adhesive interactions with nanoparticles in the solution. With this setup, we determine conditions where the oscillating fins can selectively bind, and thus, "catch" target nanoparticles within the upper fluid stream and then release these particles into the lower stream. We isolate the effects of varying the wetting interaction and the fins' oscillation modes on the effective extraction of target species from the upper stream. Our findings provide fundamental insights into the system's complex dynamics and yield guidelines for fabricating devices for the detection and separation of target molecules from complex fluids.


Bidirectional Relations between Text Reading Prosody and Reading Comprehension in the Upper Primary School Grades: A Longitudinal Perspective.
The purpose of this study was to examine the directionality of the relationship between text reading prosody and reading comprehension in the upper grades of primary school. We compared three theoretical possibilities: Two unidirectional relations from text reading prosody to reading comprehension and from reading comprehension to text reading prosody and a bidirectional relation between text reading prosody and reading comprehension. Further, we controlled for autoregressive effects and included decoding efficiency as a measure of general reading skill. Participants were 99 Dutch children, followed longitudinally, from fourth- to sixth-grade. Structural equation modeling showed that the bidirectional relation provided the best fitting model. In fifth-grade, text reading prosody was related to prior decoding and reading comprehension, whereas in sixth-grade, reading comprehension was related to prior text reading prosody. As such, the results suggest that the relation between text reading prosody and reading comprehension is reciprocal, but dependent on grade level.


Early skin-to-skin contact for mothers and their healthy newborn infants.
Mother-infant separation post birth is common. In standard hospital care, newborn infants are held wrapped or dressed in their mother's arms, placed in open cribs or under radiant warmers. Skin-to-skin contact (SSC) begins ideally at birth and should last continually until the end of the first breastfeeding. SSC involves placing the dried, naked baby prone on the mother's bare chest, often covered with a warm blanket. According to mammalian neuroscience, the intimate contact inherent in this place (habitat) evokes neuro-behaviors ensuring fulfillment of basic biological needs. This time frame immediately post birth may represent a 'sensitive period' for programming future physiology and behavior. To assess the effects of immediate or early SSC for healthy newborn infants compared to standard contact on establishment and maintenance of breastfeeding and infant physiology. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 December 2015), made personal contact with trialists, consulted the bibliography on kangaroo mother care (KMC) maintained by Dr Susan Ludington, and reviewed reference lists of retrieved studies. Randomized controlled trials that compared immediate or early SSC with usual hospital care. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Quality of the evidence was assessed using the GRADE approach. We included 46 trials with 3850 women and their infants; 38 trials with 3472 women and infants contributed data to our analyses. Trials took place in 21 countries, and most recruited small samples (just 12 trials randomized more than 100 women). Eight trials included women who had SSC after cesarean birth. All infants recruited to trials were healthy, and the majority were full term. Six trials studied late preterm infants (greater than 35 weeks' gestation). No included trial met all criteria for good quality with respect to methodology and reporting; no trial was successfully blinded, and all analyses were imprecise due to small sample size. Many analyses had statistical heterogeneity due to considerable differences between SSC and standard care control groups. Results for womenSSC women were more likely than women with standard contact to be breastfeeding at one to four months post birth, though there was some uncertainty in this estimate due to risks of bias in included trials (average risk ratio (RR) 1.24, 95% confidence interval (CI) 1.07 to 1.43; participants = 887; studies = 14; I² = 41%; GRADE: moderate quality). SSC women also breast fed their infants longer, though data were limited (mean difference (MD) 64 days, 95% CI 37.96 to 89.50; participants = 264; studies = six; GRADE:low quality); this result was from a sensitivity analysis excluding one trial contributing all of the heterogeneity in the primary analysis. SSC women were probably more likely to exclusively breast feed from hospital discharge to one month post birth and from six weeks to six months post birth, though both analyses had substantial heterogeneity (from discharge average RR 1.30, 95% CI 1.12 to 1.49; participants = 711; studies = six; I² = 44%; GRADE: moderate quality; from six weeks average RR 1.50, 95% CI 1.18 to 1.90; participants = 640; studies = seven; I² = 62%; GRADE: moderate quality).Women in the SCC group had higher mean scores for breastfeeding effectiveness, with moderate heterogeneity (IBFAT (Infant Breastfeeding Assessment Tool) score MD 2.28, 95% CI 1.41 to 3.15; participants = 384; studies = four; I² = 41%). SSC infants were more likely to breast feed successfully during their first feed, with high heterogeneity (average RR 1.32, 95% CI 1.04 to 1.67; participants = 575; studies = five; I² = 85%). Results for infantsSSC infants had higher SCRIP (stability of the cardio-respiratory system) scores overall, suggesting better stabilization on three physiological parameters. However, there were few infants, and the clinical significance of the test was unclear because trialists reported averages of multiple time points (standardized mean difference (SMD) 1.24, 95% CI 0.76 to 1.72; participants = 81; studies = two; GRADE low quality). SSC infants had higher blood glucose levels (MD 10.49, 95% CI 8.39 to 12.59; participants = 144; studies = three; GRADE: low quality), but similar temperature to infants in standard care (MD 0.30 degree Celcius (°C) 95% CI 0.13 °C to 0.47 °C; participants = 558; studies = six; I² = 88%; GRADE: low quality). Women and infants after cesarean birthWomen practicing SSC after cesarean birth were probably more likely to breast feed one to four months post birth and to breast feed successfully (IBFAT score), but analyses were based on just two trials and few women. Evidence was insufficient to determine whether SSC could improve breastfeeding at other times after cesarean. Single trials contributed to infant respiratory rate, maternal pain and maternal state anxiety with no power to detect group differences. SubgroupsWe found no differences for any outcome when we compared times of initiation (immediate less than 10 minutes post birth versus early 10 minutes or more post birth) or lengths of contact time (60 minutes or less contact versus more than 60 minutes contact). Evidence supports the use of SSC to promote breastfeeding. Studies with larger sample sizes are necessary to confirm physiological benefit for infants during transition to extra-uterine life and to establish possible dose-response effects and optimal initiation time. Methodological quality of trials remains problematic, and small trials reporting different outcomes with different scales and limited data limit our confidence in the benefits of SSC for infants. Our review included only healthy infants, which limits the range of physiological parameters observed and makes their interpretation difficult.


Behavioral profiling of NPY in aggression and neuropsychiatric diseases.
The abundantly expressed neuropeptide Y (NPY) has potent effects on feeding, body weight, and blood pressure, and exhibits important functions in various behavioral domains such as motor activity and anxiety. The potent neurotransmitter exerts its biological effects through at least five G-protein coupled receptors termed Y(1), Y(2), Y(4), Y(5), and y(6). The behavioral profile of NPY function has been extensively studied using traditional pharmacological and classic genetic animal models. Based on these studies, variations in the profile of NPY and its receptors have been found. To limit the variability and inconsistencies in the behavioral profile of NPY and to clarify its effects on certain domains in further detail, it is important to design a rational standardized strategy for behavioral testing, using a complement of different well-established and reproducible tests. This strategy can minimize the risk that false positive or false negative results lead to a contradictory and inconsistent behavioral characterization of NPY function. Ideally, such screening should be composed of an initial monitoring of general health, sensory functions, and motor abilities, before specific behavioral domains such as anxiety or aggression are investigated using a multi-tiered phenotyping approach. In this review, we will focus on a brief description of the latest insights into the behavioral profile of NPY in the selective lesser investigated domains such as aggression and depression-schizophrenia-related behaviors. We will combine this information with possible strategies to evaluate the different specific phenotypes in more detail.


DNA delivery from matrix metalloproteinase degradable poly(ethylene glycol) hydrogels to mouse cloned mesenchymal stem cells.
The ability to genetically modify mesenchymal stem cells (MSCs) seeded inside synthetic hydrogel scaffolds would offer an alternative approach to guide MSC differentiation and to study molecular pathways in three dimensions than protein delivery. In this report, we explored gene transfer to infiltrating MSCs into matrix metalloproteinase (MMP) degradable hydrogels that were loaded with DNA/poly(ethylene imine) (PEI) polyplexes. DNA/PEI polyplexes were encapsulated inside poly(ethylene glycol) (PEG) hydrogels crosslinked with MMP-degradable peptides via Michael addition chemistry. A large fraction of encapsulated polyplexes remained active after encapsulation (65%) and the mechanical properties of the hydrogels were unchanged by the encapsulation of the polyplexes. Cells were seeded inside the hydrogel scaffolds using two different approaches: clustered and homogeneous. The viability of MSCs was similar in hydrogels with and without polyplexes. Transgene expression was characterized with time using a secreted reporter gene and showed different profiles for clustered and homogeneously seeded cells. Clustered cells resulted in cumulative transgene expression that increased through the 21-day incubation, while homogeneously seeded cells resulted in cumulative transgene expression that plateaued after 7 days of culture. The use of hydrogel scaffolds that allow cellular infiltration to deliver DNA may result in long lasting signals in vivo, which are essential for the regeneration of functional tissues.


A review of factors influencing the stress response in Australian marsupials.
Many Australian marsupials are threatened species. In order to manage in situ and ex situ populations effectively, it is important to understand how marsupials respond to threats. Stress physiology (the study of the response of animals to challenging stimuli), a key approach in conservation physiology, can be used to characterize the physiological response of wildlife to threats. We reviewed the literature on the measurement of glucocorticoids (GCs), endocrine indicators of stress, in order to understand the stress response to conservation-relevant stressors in Australian marsupials and identified 29 studies. These studies employed a range of methods to measure GCs, with faecal glucocorticoid metabolite enzyme immunoassay being the most common method. The main stressors considered in studies of marsupials were capture and handling. To date, the benefits of stress physiology have yet to be harnessed fully in marsupial conservation. Despite a theoretical base dating back to the 1960s, GCs have only been used to understand how 21 of the 142 extant species of Australian marsupial respond to stressors. These studies include merely six of the 60 marsupial species of conservation concern (IUCN Near Threatened to Critically Endangered). Furthermore, the fitness consequences of stress for Australian marsupials are rarely examined. Individual and species differences in the physiological stress response also require further investigation, because significant species-specific variations in GC levels in response to stressors can shed light on why some individuals or species are more vulnerable to stress factors while others appear more resilient. This review summarizes trends, knowledge gaps and future research directions for stress physiology research in Australian marsupial conservation.


C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation.
Traumatic brain injury (TBI) induces a strong inflammatory response which includes blood-brain barrier damage, edema formation and infiltration of different immune cell subsets. More recently, microvascular thrombosis has been identified as another pathophysiological feature of TBI. The contact-kinin system represents an interface between inflammatory and thrombotic circuits and is activated in different neurological diseases. C1-Inhibitor counteracts activation of the contact-kinin system at multiple levels. We investigated the therapeutic potential of C1-Inhibitor in a model of TBI. Male and female C57BL/6 mice were subjected to cortical cryolesion and treated with C1-Inhibitor after 1 h. Lesion volumes were assessed between day 1 and day 5 and blood-brain barrier damage, thrombus formation as well as the local inflammatory response were determined post TBI. Treatment of male mice with 15.0 IU C1-Inhibitor, but not 7.5 IU, 1 h after cryolesion reduced lesion volumes by ~75% on day 1. This protective effect was preserved in female mice and at later stages of trauma. Mechanistically, C1-Inhibitor stabilized the blood-brain barrier and decreased the invasion of immune cells into the brain parenchyma. Moreover, C1-Inhibitor had strong antithrombotic effects. C1-Inhibitor represents a multifaceted anti-inflammatory and antithrombotic compound that prevents traumatic neurodegeneration in clinically meaningful settings.


Comparing a supervised and an unsupervised classification method for burst detection in neonatal EEG.
Hidden Markov Models (HMM) and Support Vector Machines (SVM) using unsupervised and supervised training, respectively, were compared with respect to their ability to correctly classify burst and suppression in neonatal EEG. Each classifier was fed five feature signals extracted from EEG signals from six full term infants who had suffered from perinatal asphyxia. Visual inspection of the EEG by an experienced electroencephalographer was used as the gold standard when training the SVM, and for evaluating the performance of both methods. The results are presented as receiver operating characteristic (ROC) curves and quantified by the area under the curve (AUC). Our study show that the SVM and the HMM exhibit similar performance, despite their fundamental differences.


Anthelmintic resistance in cyathostomin populations from horse yards in Italy, United Kingdom and Germany.
A large survey was carried out in 2008 in Europe to evaluate the efficacy of fenbendazole (FBZ), pyrantel (PYR), ivermectin (IVM) and moxidectin (MOX), i.e. the major anthelmintic molecules used in current practice against cyathostomins affecting horses. A total of 102 yards and 1704 horses was studied in three countries: 60 yards and 988 horses from Italy, 22 and 396 from the UK, 20 and 320 from Germany. The survey consisted of Faecal Egg Count Reduction Tests (FECRTs) with a faecal egg count reduction (FECR) categorization of (I) resistance present if FECR <90% and the lower 95% confidence limit (LCL) <90%, (II) resistance suspected if FECR >/= 90% and/or LCL <90% and (III) no resistance if FECR >/= 90% and LCL >90%. The calculation of FECR data was performed employing bootstrap analysis of group arithmetic means. The testing of FBZ on a total of 80 yards resulted in resistance present on more than 80% of the UK and German yards and on significantly fewer in Italy, i.e. in 38% (p < 0.01). PYR, IVM and MOX were tested on a total of 102 yards. For PYR resistance present was found in 25% of the yards with no significant differences between countries. For IVM resistance present was encountered in one Italian and two UK yards (3%), resistance present to MOX was not found in any yard in any country. The results indicate that single and/or multiple drug resistance in equine cyathostomins is present in the three countries, is widespread particularly for FBZ and/or PYR and in one UK yard multiple resistance present was detected to FBZ, PYR and IVM. Macrocylic lactones proved to be the most effective drugs, with some evidence of resistance to IVM and highest activity of MOX, despite a single case of reduced efficacy in Germany. These data call for the development and implementation, among practitioners, owners and managers, of further plans to reduce the expansion of the anthelmintic resistant populations and to use those anthelmintics that remain effective in a manner that preserves their efficacy as long as possible.


Predicting Hydration Free Energies of the FreeSolv Database of Drug-like Molecules with Molecular Density Functional Theory.
We assess the performance of molecular density functional theory (MDFT) to predict hydration free energies of the small drug-like molecules benchmark, FreeSolv. The MDFT in the hypernetted chain approximation (HNC) coupled with a pressure correction predicts experimental hydration free energies of the FreeSolv database within 1 kcal/mol with an average computation time of 2 cpu·min per molecule. This is the same accuracy as for simulation-based free energy calculations that typically require hundreds of cpu·h or tens of gpu·h per molecule.


Geographical variation in bill size across bird species provides evidence for Allen's rule.
Allen's rule proposes that the appendages of endotherms are smaller, relative to body size, in colder climates, in order to reduce heat loss. Empirical support for Allen's rule is mainly derived from occasional reports of geographical clines in extremity size of individual species. Interspecific evidence is restricted to two studies of leg proportions in seabirds and shorebirds. We used phylogenetic comparative analyses of 214 bird species to examine whether bird bills, significant sites of heat exchange, conform to Allen's rule. The species comprised eight diverse taxonomic groups-toucans, African barbets, Australian parrots, estrildid finches, Canadian galliforms, penguins, gulls, and terns. Across all species, there were strongly significant relationships between bill length and both latitude and environmental temperature, with species in colder climates having significantly shorter bills. Patterns supporting Allen's rule in relation to latitudinal or altitudinal distribution held within all groups except the finches. Evidence for a direct association with temperature was found within four groups (parrots, galliforms, penguins, and gulls). Support for Allen's rule in leg elements was weaker, suggesting that bird bills may be more susceptible to thermoregulatory constraints generally. Our results provide the strongest comparative support yet published for Allen's rule and demonstrate that thermoregulation has been an important factor in shaping the evolution of bird bills.


BREEDING AND GENETICS SYMPOSIUM: Climate change and selective breeding in aquaculture.
Aquaculture is the fastest growing food production sector and it contributes significantly to global food security. Based on Food and Agriculture Organization (FAO) of the United Nations, aquaculture production must increase significantly to meet the future global demand for aquatic foods in 2050. According to Intergovernmental Panel on Climate Change (IPCC) and FAO, climate change may result in global warming, sea level rise, changes of ocean productivity, freshwater shortage, and more frequent extreme climate events. Consequently, climate change may affect aquaculture to various extents depending on climatic zones, geographical areas, rearing systems, and species farmed. There are 2 major challenges for aquaculture caused by climate change. First, the current fish, adapted to the prevailing environmental conditions, may be suboptimal under future conditions. Fish species are often poikilothermic and, therefore, may be particularly vulnerable to temperature changes. This will make low sensitivity to temperature more important for fish than for livestock and other terrestrial species. Second, climate change may facilitate outbreaks of existing and new pathogens or parasites. To cope with the challenges above, 3 major adaptive strategies are identified. First, general 'robustness' will become a key trait in aquaculture, whereby fish will be less vulnerable to current and new diseases while at the same time thriving in a wider range of temperatures. Second, aquaculture activities, such as input power, transport, and feed production contribute to greenhouse gas emissions. Selection for feed efficiency as well as defining a breeding goal that minimizes greenhouse gas emissions will reduce impacts of aquaculture on climate change. Finally, the limited adoption of breeding programs in aquaculture is a major concern. This implies inefficient use of resources for feed, water, and land. Consequently, the carbon footprint per kg fish produced is greater than when fish from breeding programs would be more heavily used. Aquaculture should use genetically improved and robust organisms not suffering from inbreeding depression. This will require using fish from well-managed selective breeding programs with proper inbreeding control and breeding goals. Policymakers and breeding organizations should provide incentives to boost selective breeding programs in aquaculture for more robust fish tolerating climatic change.


Dynamics and control of Ebola virus transmission in Montserrado, Liberia: a mathematical modelling analysis.
A substantial scale-up in public health response is needed to control the unprecedented Ebola virus disease (EVD) epidemic in west Africa. Current international commitments seek to expand intervention capacity in three areas: new EVD treatment centres, case ascertainment through contact tracing, and household protective kit allocation. We aimed to assess how these interventions could be applied individually and in combination to avert future EVD cases and deaths. We developed a transmission model of Ebola virus that we fitted to reported EVD cases and deaths in Montserrado County, Liberia. We used this model to assess the effectiveness of expanding EVD treatment centres, increasing case ascertainment, and allocating protective kits for controlling the outbreak in Montserrado. We varied the efficacy of protective kits from 10% to 50%. We compared intervention initiation on Oct 15, 2014, Oct 31, 2014, and Nov 15, 2014. The status quo intervention was defined in terms of case ascertainment and capacity of EVD treatment centres on Sept 23, 2014, and all behaviour and contact patterns relevant to transmission as they were occurring at that time. The primary outcome measure was the expected number of cases averted by Dec 15, 2014. We estimated the basic reproductive number for EVD in Montserrado to be 2·49 (95% CI 2·38-2·60). We expect that allocating 4800 additional beds at EVD treatment centres and increasing case ascertainment five-fold in November, 2014, can avert 77 312 (95% CI 68 400-85 870) cases of EVD relative to the status quo by Dec 15, 2014. Complementing these measures with protective kit allocation raises the expectation as high as 97 940 (90 096-105 606) EVD cases. If deployed by Oct 15, 2014, equivalent interventions would have been expected to avert 137 432 (129 736-145 874) cases of EVD. If delayed to Nov 15, 2014, we expect the interventions will at best avert 53 957 (46 963-60 490) EVD cases. The number of beds at EVD treatment centres needed to effectively control EVD in Montserrado substantially exceeds the 1700 pledged by the USA to west Africa. Accelerated case ascertainment is needed to maximise effectiveness of expanding the capacity of EVD treatment centres. Distributing protective kits can further augment prevention of EVD, but it is not an adequate stand-alone measure for controlling the outbreak. Our findings highlight the rapidly closing window of opportunity for controlling the outbreak and averting a catastrophic toll of EVD cases and deaths. US National Institutes of Health.


Primary SARS-CoV-2 Pneumonia Screening in Adults: Analysis of the Correlation Between High-Resolution Computed Tomography Pulmonary Patterns and Initial Oxygen Saturation Levels.
Chest High-Resolution Computed Tomography (HRCT) is mandatory for patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and a high Respiratory Rate (RR) because sublobar consolidation is the likely pathological pattern in addition to Ground Glass Opacities (GGOs). The present study determined the correlation between the percentage extent of typical pulmonary lesions on HRCT, as a representation of severity, and the RR and peripheral oxygen saturation level (SpO2), as measured through pulse oximetry, in patients with Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-confirmed primary (noncomplicated) SARS-CoV-2 pneumonia. The present retrospective study was conducted in 332 adult patients who presented with dyspnea and hypoxemia and were admitted to Prince Mohammed bin Abdulaziz Hospital, Riyadh, Saudi Arabia between May 15, 2020 and December 15, 2020. All the patients underwent chest HRCT. Of the total, 198 patients with primary noncomplicated SARS-CoV-2 pneumonia were finally selected based on the typical chest HRCT patterns. The main CT patterns, GGO and sublobar consolidation, were individually quantified as a percentage of the total pulmonary involvement through algebraic summation of the percentage of the 19 pulmonary segments affected. Additionally, the statistical correlation strength between the total percentage pulmonary involvement and the age, initial RR, and percentage SpO2 of the patients was determined. The mean ± Standard Deviation (SD) age of the 198 patients was 48.9 ± 11.4 years. GGO magnitude alone exhibited a significant weak positive correlation with patients' age (r = 0.2; p = 0.04). Sublobar consolidation extent exhibited a relatively stronger positive correlation with RR than GGO magnitude (r = 0.23; p = 0.002). A relatively stronger negative correlation was observed between the GGO extent and SpO2 (r = - 0.38; p = 0.002) than that between sublobar consolidation and SpO2 (r = - 0.2; p = 0.04). An increase in the correlation strength was demonstrated with increased case segregation with GGO extent (r = - 0.34; p = 0.01). The correlation between the magnitudes of typical pulmonary lesion patterns, particularly GGO, which exhibited an incremental correlation pattern on chest HRCT, and the SpO2 percentage, may allow the establishment of an artificial intelligence program to differentiate primary SARS-CoV-2 pneumonia from other complications and associated pathology influencing SpO2.


A hydrophobic domain in the large envelope protein is essential for fusion of duck hepatitis B virus at the late endosome.
The duck hepatitis B virus (DHBV) envelope is comprised of two transmembrane (TM) proteins, the large (L) and the small (S), that assemble into virions and subviral particles. Secondary-structure predictions indicate that L and S have three alpha-helical, membrane-spanning domains, with TM1 predicted to act as the fusion peptide following endocytosis of DHBV into the hepatocyte. We used bafilomycin A1 during infection of primary duck hepatocytes to show that DHBV must be trafficked from the early to the late endosome for fusion to occur. Alanine substitution mutations in TM1 of L and S, which lowered TM1 hydrophobicity, were used to examine the role of TM1 in infectivity. The high hydrophobicity of the TM1 domain of L, but not of S, was shown to be essential for virus infection at a step downstream of receptor binding and virus internalization. Using wild-type and mutant synthetic peptides, we demonstrate that the hydrophobicity of this domain is required for the aggregation and the lipid mixing of phospholipid vesicles, supporting the role of TM1 as the fusion peptide. While lipid mixing occurred at pH 7, the kinetics of insertion of the fusion peptide was increased at pH 5, consistent with the location of DHBV in the late-endosome compartment and previous studies of the nonessential role of low pH for infectivity. Exchange of the TM1 of DHBV with that of hepatitis B virus yielded functional, infectious DHBV particles, suggesting that TM1 of all of the hepadnaviruses act similarly in the fusion mechanism.


Capacity of forensic patients to consent to research: the use of the MacCAT-CR.
The ability of psychiatric patients and prisoners to provide informed consent to participate in clinical research has given rise to much debate. Forensic psychiatric patients present a particular concern regarding their competence to consent to research, as they are both patients and prisoners. The primary goal of this research was to evaluate whether, by employing structured assessments of capacity to consent to research, we could determine if this combined vulnerability leads to differences in competence from the published abilities of nonforensic psychiatric patients. Subjects deemed incapable of providing informed consent scored differently and lower than the other consent groups on three aspects of the decision-making process. Diagnosis evidenced only a slight relationship to decision-making abilities, and this difference was only in the ability to understand the basic procedural elements of the research. Psychiatric symptoms were modestly related to decision-making. Positive symptoms were associated with poorer performance on the Understanding subscale of the MacCAT-CR, and negative symptoms were associated with lowered performance on the Reasoning subscale. These results are in accord with several published studies of nonforensic psychiatric patients and suggest that concerns regarding both forensic and nonforensic psychiatric patients' ability to provide informed consent may be unwarranted, especially in patients with few active symptoms.


The ubiquitin ligase mLin41 temporally promotes neural progenitor cell maintenance through FGF signaling.
How self-renewal versus differentiation of neural progenitor cells is temporally controlled during early development remains ill-defined. We show that mouse Lin41 (mLin41) is highly expressed in neural progenitor cells and its expression declines during neural differentiation. Loss of mLin41 function in mice causes reduced proliferation and premature differentiation of embryonic neural progenitor cells. mLin41 was recently implicated as the E3 ubiquitin ligase that mediates degradation of Argonaute 2 (AGO2), a key effector of the microRNA pathway. However, our mechanistic studies of neural progenitor cells indicate mLin41 is not required for AGO2 ubiquitination or stability. Instead, mLin41-deficient neural progenitors exhibit hyposensitivity for fibroblast growth factor (FGF) signaling. We show that mLin41 promotes FGF signaling by directly binding to and enhancing the stability of Shc SH2-binding protein 1 (SHCBP1) and that SHCBP1 is an important component of FGF signaling in neural progenitor cells. Thus, mLin41 acts as a temporal regulator to promote neural progenitor cell maintenance, not via the regulation of AGO2 stability, but through FGF signaling.


PCBP1 and PCBP2 both bind heavily oxidized RNA but cause opposing outcomes, suppressing or increasing apoptosis under oxidative conditions.
PCBP1, a member of the poly(C)-binding protein (PCBP) family, has the capability of binding heavily oxidized RNA and therefore participates in the cellular response to oxidative conditions, helping to induce apoptosis. There are four other members of this family, PCBP2, PCBP3, PCBP4, and hnRNPK, but it is not known whether they play similar roles. To learn more, we first tested their affinity for an RNA strand carrying two 8-oxoguanine (8-oxoG) residues at sites located in close proximity to each other, representative of a heavily oxidized strand or RNA with one 8-oxoG or none. Among them, only PCBP2 exhibited highly selective binding to RNA carrying two 8-oxoG residues similar to that observed with PCBP1. In contrast, PCBP3, PCBP4, and hnRNPK bound RNA with or without 8-oxoG modifications and exhibited slightly increased binding to the former. Mutations in conserved RNA-binding domains of PCBP2 disrupted the specific interaction with heavily oxidized RNA. We next tested PCBP2 activity in cells. Compared with WT HeLa S3 cells, PCBP2-KO cells established by gene editing exhibited increased apoptosis with increased caspase-3 activity and PARP1 cleavage under oxidative conditions, which were suppressed by the expression of WT PCBP2 but not one of the mutants lacking binding activity. In contrast, PCBP1-KO cells exhibited reduced apoptosis with much less caspase-3 activity and PARP cleavage than WT cells. Our results indicate that PCBP2 as well as PCBP1 bind heavily oxidized RNA; however, the former may counteract PCBP1 to suppress apoptosis under oxidative conditions.


Tattooing in prisons--not such a pretty picture.
Tattooing in prison represents a unique combination of risk factors for blood borne virus (BBV) transmission because it is illicitly performed by untrained operators with homemade, unsterile, and frequently-shared equipment. It occurs in a setting where a high proportion of people are already infected with hepatitis C virus (HCV) and other BBVs. This study measured the frequency of tattoo acquisition by prisoners inside and outside prison, and the associations between tattooing, injecting drug use, and HCV infection risk. A cross-sectional survey was conducted in correctional facilities in Victoria, Australia. Participants completed a questionnaire that asked about injecting drug use and tattooing and provided a finger-prick blood sample that was tested for HCV antibody. Six hundred and forty-two prisoners participated in the study; 449 had ever been tattooed, of whom 182 (41%) had been tattooed in adult or juvenile prison. Of the participants who were not tattooed professionally, 27% reported someone using the same needle, and 42% reported someone had used the ink before them. Prisoners with a history of drug injection were more likely to have a tattoo and to have acquired a tattoo in prison (OR 3.0; CI 1.7-5.4). The HCV antibody-positive prisoners were more likely to have acquired a tattoo in prison compared with HCV antibody-negative prisoners. Acquiring a tattoo in prison was common and the reports of sharing the tattooing needle and ink was high, placing prisoners at risk of acquiring HCV through tattooing in prison. Trials need to be undertaken that evaluate the risk and benefits of legal tattoos in prison.


Prevalence, incidence, and treatments of Dupuytren's disease in the United States: results from a population-based study.
This large population-based study was conducted to estimate the prevalence of Dupuytren's disease in US adults and describe associated treatment patterns. A total of 23,103 individuals from an Internet-based research panel representative of the US population completed a brief online survey designed to identify individuals with symptoms, diagnoses, and/or treatment experience indicative of Dupuytren's disease (mean age = 50 years). The prevalence of Dupuytren's disease defined as a self-reported physician diagnosis and/or surgical treatment was estimated as 1% (95% CI = 0.8-1.2), but the estimated prevalence is much higher (7.3%) when including self-reported symptoms of ropelike growth or hard bumps on the hand. The annual incidence proportion was estimated at about 3 cases per 10,000 adults. A total of 326 participants who reported relevant Dupuytren's symptoms, treatment, and/or diagnosis completed a more in-depth survey focusing on timing of medical treatments after first symptom noticed, description of functional impairment, treatment patterns, and family history. From the second survey, most patients who reported seeking treatment for hand symptoms initially saw a primary care physician, and the mean time from noticing the first hand symptom to seeing a doctor was 23.1 months. At their first doctor visit for hand symptoms, only 9% of patients received a diagnosis of Dupuytren's disease and 48% were advised to "wait and see" or received no treatment. Results from the current study indicate a number of unmet medical needs, so strategies to raise physician awareness of disease symptoms and effective treatment options may be helpful.


Microglial interactions with synapses are modulated by visual experience.
Microglia are the immune cells of the brain. In the absence of pathological insult, their highly motile processes continually survey the brain parenchyma and transiently contact synaptic elements. Aside from monitoring, their physiological roles at synapses are not known. To gain insight into possible roles of microglia in the modification of synaptic structures, we used immunocytochemical electron microscopy, serial section electron microscopy with three-dimensional reconstructions, and two-photon in vivo imaging to characterize microglial interactions with synapses during normal and altered sensory experience, in the visual cortex of juvenile mice. During normal visual experience, most microglial processes displayed direct apposition with multiple synapse-associated elements, including synaptic clefts. Microglial processes were also distinctively surrounded by pockets of extracellular space. In terms of dynamics, microglial processes localized to the vicinity of small and transiently growing dendritic spines, which were typically lost over 2 d. When experience was manipulated through light deprivation and reexposure, microglial processes changed their morphology, showed altered distributions of extracellular space, displayed phagocytic structures, apposed synaptic clefts more frequently, and enveloped synapse-associated elements more extensively. While light deprivation induced microglia to become less motile and changed their preference of localization to the vicinity of a subset of larger dendritic spines that persistently shrank, light reexposure reversed these behaviors. Taken together, these findings reveal different modalities of microglial interactions with synapses that are subtly altered by sensory experience. These findings suggest that microglia may actively contribute to the experience-dependent modification or elimination of a specific subset of synapses in the healthy brain.


Strategies for nevirapine initiation in HIV-infected children taking pediatric fixed-dose combination "baby pills" in Zambia: a randomized controlled trial.
Fixed-dose combination scored dispersible stavudine, lamivudine, and nevirapine minitablets (Triomune Baby and Junior; Cipla Ltd) are simpler and cheaper than liquid formulations and have correct dose ratios for human immunodeficiency virus-infected children. However, they cannot be used for dose escalation (DE) of nevirapine. Children were randomized to initiate antiretroviral therapy with full-dose (FD) nevirapine (Triomune Baby or Junior in the morning and evening) versus DE (half-dose nevirapine for 14 days [Triomune in the morning and stavudine-lamivudine {Lamivir-S} in the evening], then FD), in accordance with World Health Organization weight-band dosing tables. The primary end point was nevirapine-related clinical or laboratory grade 3 or 4 adverse events (AEs). In total, 211 children (median [interquartile range {IQR}] age, 5 [ 2-9 ] years; median [IQR] CD4 cell percentage, 13% [8%-18%]) were enrolled and followed up for a median (IQR) of 92 (68-116) weeks. There were 31 grade 3 or 4 AEs that were definitely/probably or uncertainly related to nevirapine in the FD group (18.0 per 100 child-years), compared with 29 in the DE group (16.5 per 100 child-years) (incidence rate ratio, 1.09; 95% confidence interval, 0.63–1.87; P = .74). All were asymptomatic; 11 versus 3 were single grade 3 or 4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, all of which resolved without a change in nevirapine dose or interruption. Thirteen (12%) FD versus 2 (2%) DE children had grade 1 (2 in FD) or grade 2 (11 in FD and 2 in DE) rashes. Three (2 in FD and 1 in DE) substituted efavirenz, 3 (FD) continued FD nevirapine, and 9 (8 in FD and 1 in DE) temporarily interrupted nevirapine, followed by successful DE. Predictors of nevirapine rash were older age (P = .003) and higher CD4 cell count for age (P = .03). Twenty-two children died (12 in FD and 10 in DE), 1 FD and 5 DE children at <4 weeks; none were considered to be drug related by independent review. Rash was more frequent with FD nevirapine, but 88% had no clinical toxicity; elevated AST or ALT levels were transient and resolved spontaneously, suggesting that routine laboratory monitoring has limited value. Dual pediatric stavudine-lamivudine minitablets are preferred for safe and simple DE; if unavailable, initiating FD Triomune requires timely review for rash, which could be managed by temporary reduction to half-dose Triomune or efavirenz substitution. Current Controlled Trials identifier: ISRCTN31084535 .


Liver and spleen elastography using supersonic shear imaging for the non-invasive diagnosis of cirrhosis severity and oesophageal varices.
Elastography is a promising non-invasive approach for assessing liver fibrosis. We assessed diagnostic performances of liver and spleen stiffness using supersonic shear imaging for diagnosing cirrhosis severity and oesophageal varices. 401 consecutive cirrhotic patients were prospectively enrolled from November 2012 to March 2014. All patients underwent liver and spleen stiffness measurement with supersonic shear imaging and Fibroscan. Failures of measurement were 6.2% and 29.2% for liver and spleen stiffness (supersonic shear imaging), and 18.4% for liver stiffness (Fibroscan). Liver and spleen stiffness were correlated with severity of cirrhosis, with values increasing according to Child-Pugh subclasses and presence of complications. With a negative predictive value ≥90%, liver stiffness cut-offs for high-risk oesophageal varices, history of ascites, Child-Pugh B/C, variceal bleeding and clinical decompensation were 12.8, 19, 21.4, 30.5, and 39.4 kPa, respectively. Areas under the curve of spleen and liver stiffness (supersonic shear imaging), and liver stiffness (Fibroscan) were 0.80, 0.77 and 0.73 respectively for detection of oesophageal varices. Liver stiffness using supersonic shear imaging is a relevant diagnostic tool for assessing cirrhosis severity and its complications. Spleen stiffness shows promising results for the detection of oesophageal varices but is not yet sufficiently robust for clinical practice owing to high failure rates.


The anti-atherosclerotic effect of olive leaf extract is related to suppressed inflammatory response in rabbits with experimental atherosclerosis.
The anti-atherogenic effect of olive leaf extract is supposed to be related to its activities of anti-oxidation and anti-inflammation. To prove the effect of anti-atherosclerosis by olive leaf extract (OLE) and to elucidate the mechanism behind. Twenty-four rabbits were assigned to the control, high lipid diet (HLD) and OLE group that were fed with standard diet, HLD and HLD supplemented with OLE, respectively. Serum levels of atherosclerosis related markers, triglyceride (TG), total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and malondialdehyde (MDA) were detected at the ends of week 2, 4 and 6. Surface lesions and thickness of intimas were measured at the end of week6. The protein and/or mRNA expressions of inflammation factors, monocyte chemoattractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, nuclear factor-kappa B (NF-kappaB) and tumor necrosis factor alpha (TNF-alpha) were investigated by immunohistochemistry and RT-PCR. Atherosclerotic lesions were found in the HLD and OLE groups but not in the control group. In comparison with that in the HLD group, reduced size and thickness of intima (0.31 +/- 0.26 in the HLD group versus 0.10 +/- 0.03 mm in the OLE group) were found in the OLE group. The MDA level, an indicator of antioxidant status, was 35.27 +/- 15.37 in the HLD group and 20.63 +/- 11.52 nmol/ml in the OLE group. The level of CHO, TG and LDL-C were 104.46 +/- 30.34, 2.48 +/- 1.11, 82.83 +/- 28.44 mmol/l in the HLD group versus 83.03 +/- 27.23, 1.84 +/- 0.44, 59.51 +/- 23.72 mmol/l in the OLE group. Down-regulated expressions of MCP-1, VCAM-1, NF-kappaB and TNF-alpha at both protein and mRNA level (P < 0.05) were also found with the administration of OLE. This study proved the effect of OLE on inhibition of atherosclerosis, which is related to the suppressed inflammatory response.


Modulating the Copper-Sulfur Interaction in Type 1 Blue Copper Azurin by Replacing Cys112 with Nonproteinogenic Homocysteine.
The Cu-SCys interaction is known to play a dominant role in defining the type 1 (T1) blue copper center with respect to both its electronic structure and electron transfer function. Despite this importance, its role has yet to be probed by mutagenesis studies without dramatic change of its T1 copper character. We herein report replacement of the conserved Cys112 in azurin with the nonproteinogenic amino acid homocysteine. Based on electronic absorption, electron paramagnetic resonance, and extended x-ray absorption fine structural spectroscopic studies, this variant displays typical type 1 copper site features. Surprisingly, instead of increasing the strength of the Cu-sulfur interaction by the introduction of the extra methylene group, the Cys112Hcy azurin showed a decrease in the covalent interaction between SHcy and Cu(II) when compared with the WT SCys-Cu(II) interaction. This is likely due to geometric adjustment of the center that resulted in the copper ion moving out of the trigonal plane defined by two histidines and one Hcy and closer to Met121. These structural changes resulted in an increase of reduction potential by 35 mV, consistent with lower Cu-S covalency. These results suggest that the Cu-SCys interaction is close to being optimal in native blue copper protein. It also demonstrates the power of using nonproteinogenic amino acids in addressing important issues in bioinorganic chemistry.


Deceased-donor kidney transplantation: improvement in long-term survival.
Despite marked improvement in short-term renal allograft survival rates (GSR) in recent years, improvement in long-term GSR remained elusive. We analysed the kidney transplant experience at our centre accrued over four decades to evaluate how short-term and long-term GSR had changed and to identify risk factors affecting graft survival. The study included 1476 adult recipients of a deceased-donor kidney transplant who were transplanted between 1963 and 2006 and who had received one of five distinct immunosuppressive protocols. Five-year actual GSR steadily improved over the years as immunosuppressive therapy evolved (22-86%, P < 0.001) in spite of an increasing trend in the transplantation of higher-risk donor-recipient pairings. For those whose grafts functioned for the first year, subsequent 4-year GSR (5-year conditional GSR) also improved significantly (63-92%, P < 0.001). Acute rejection and delayed graft function (DGF) were the most significant risk factors for actual graft survival, while acute rejection was the only significant risk factor for conditional GSR. Use of kidneys from expanded-criteria donors (ECD) was not a risk factor, compared to the use of standard-criteria donor kidneys for either 5-year actual or conditional GSR. There was an impressive decline in the incidence of acute rejection events (77.4-5.8%, P < 0.001). While the DGF rate had decreased, it still remained high (68.7-38.5%, P < 0.001). We found a significant improvement in both short-term and long-term GSR of deceased-donor kidney transplants over the last four decades. These improvements are most likely related to the decreased incidence of acute rejection episodes. Minimizing acute rejection events and preventing DGF could result in further improvement in the GSR. Our experience in the judicious use of ECD kidneys suggests that this source of kidneys could be expanded further.


Increased platelet count and leucocyte-platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis.
The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference. A full blood count was done and whole blood flow cytometry used to measure platelet surface expression of CD62P, CD63, and PAC1 binding and the percentage of leucocyte-platelet complexes in patients with acute (0-21 days, n = 19) and convalescent (79-365 days) symptomatic (n = 16) and asymptomatic (n = 16) severe (> or =70%) carotid stenosis. Most patients were treated with aspirin (37.5-300 mg daily) although alternative antithrombotic regimens were more commonly used in the symptomatic group. The mean platelet count was higher in patients with acute and convalescent symptomatic compared with asymptomatic carotid stenosis. There were no significant differences in the median percentage expression of CD62P and CD63, or PAC1 binding between the acute or convalescent symptomatic and asymptomatic patients. The median percentages of neutrophil-platelet (p = 0.004), monocyte-platelet (p = 0.046), and lymphocyte-platelet complexes (p = 0.02) were higher in acute symptomatic than in asymptomatic patients. In patients on aspirin monotherapy, the percentages of neutrophil-platelet and monocyte-platelet complexes (p = 0.03) were higher in acute symptomatic (n = 11) than asymptomatic patients (n = 14). In the convalescent phase, the median percentages of all leucocyte-platelet complexes in the symptomatic group dropped to levels similar to those found in the asymptomatic group. Increased platelet count and leucocyte-platelet complex formation may contribute to the early excess risk of stroke in patients with recently symptomatic carotid stenosis.


Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes.
The aim of the present study was to determine whether the endothelial dysfunction associated with CAD (coronary artery disease) and T2D (Type 2 diabetes mellitus) is concomitant with elevated mtROS (mitochondrial reactive oxygen species) production in the endothelium and establish if this, in turn, regulates the activity of endothelial AMPK (AMP-activated protein kinase). We investigated endothelial function, mtROS production and AMPK activation in saphenous veins from patients with advanced CAD. Endothelium-dependent vasodilation was impaired in patients with CAD and T2D relative to those with CAD alone. Levels of mitochondrial H(2)O(2) and activity of AMPK were significantly elevated in primary HSVECs (human saphenous vein endothelial cells) from patients with CAD and T2D compared with those from patients with CAD alone. Incubation with the mitochondria-targeted antioxidant, MitoQ(10) significantly reduced AMPK activity in HSVECs from patients with CAD and T2D but not in cells from patients with CAD alone. Elevated mtROS production in the endothelium of patients with CAD and T2D increases AMPK activation, supporting a role for the kinase in defence against oxidative stress. Further investigation is required to determine whether pharmacological activators of AMPK will prove beneficial in the attenuation of endothelial dysfunction in patients with CAD and T2D.


Pregnancies of unknown location after in vitro fertilization: minimally invasive management with Karman cannula aspiration.
To describe a standardized protocol for the assessment of asymptomatic patients with pregnancies of unknown location (PUL) after IVF. Retrospective cohort study. University-based infertility clinic. Women undergoing fresh IVF/intracytoplasmic sperm injection (ICSI) cycles between 2005 and 2011. Endometrial sampling using Karman suction cannula in patients with PUL and abnormal β-hCG trend (increase <53% or decrease <15% in 2 days) and a pelvic ultrasound unremarkable for an intrauterine pregnancy (IUP) or an ectopic pregnancy (EP). Proportion of patients spared methotrexate (MTX) administration. Endometrial sampling was performed in 45 patients. Of these, 31 (68.9%) were diagnosed with failed IUP by either a sampling after the β-hCG decline (≥15%) and/or the presence of villi on final pathology. No further intervention was required. Fourteen patients (31.1%) were diagnosed with presumed EP by persistent β-hCG level after negative pathology. Ten of these patients (71%) were successfully treated with a single dose of MTX; three required an additional dose, and one required laparoscopy for a ruptured EP. In asymptomatic patients with PUL and abnormal β-hCG trends after IVF, the utility of Karman aspiration to confirm an IUP may obviate treatment with MTX in more than two-thirds of patients.


Rapid-cycling populations of brassica.
Rapid-cycling populations of six economically important species in the genus Brassica have unusual potential for resolving many problems in plant biology and for use in education. Rapid-cycling brassicas can produce up to ten generations of seed per year and serve as models for research in genetics, host-parasite relations, molecular biology, cell biology, plant biochemistry, population biology, and plant breeding. Brassicas are a highly diverse group of crop plants that have great economic value as vegetables and as sources of condiment mustard, edible and industrial oil, animal fodder, and green manure. These plants can also be used in the classroom as convenient, rapidly responding, living plant materials for "hands on" learning at all levels of our educational system.


Global economic potential for reducing carbon dioxide emissions from mangrove loss.
Mangroves are among the most threatened and rapidly disappearing natural environments worldwide. In addition to supporting a wide range of other ecological and economic functions, mangroves store considerable carbon. Here, we consider the global economic potential for protecting mangroves based exclusively on their carbon. We develop unique high-resolution global estimates (5' grid, about 9 × 9 km) of the projected carbon emissions from mangrove loss and the cost of avoiding the emissions. Using these spatial estimates, we derive global and regional supply curves (marginal cost curves) for avoided emissions. Under a broad range of assumptions, we find that the majority of potential emissions from mangroves could be avoided at less than $10 per ton of CO(2). Given the recent range of market price for carbon offsets and the cost of reducing emissions from other sources, this finding suggests that protecting mangroves for their carbon is an economically viable proposition. Political-economy considerations related to the ability of doing business in developing countries, however, can severely limit the supply of offsets and increases their price per ton. We also find that although a carbon-focused conservation strategy does not automatically target areas most valuable for biodiversity, implementing a biodiversity-focused strategy would only slightly increase the costs.


A snapshot of the scope of obesity prevention practice in Australia.
Community-based initiatives (CBIs) that build capacity and promote healthy environments hold promise for preventing obesity and non-communicable disease, however their characteristics remain poorly understood and lessons are learned in isolation. This limits understanding of likely effectiveness of CBIs; the potential for actively supporting practice; and the translation of community-based knowledge into policy. Building on an initial survey (2010), an online survey was launched (2013) with the aim to describe the reach and characteristics of Australian CBIs and identify and evaluate elements known to contribute to best practice, effectiveness and sustainability. Responses from 104 CBIs were received in 2013. Geographic location generally reflected population density in Australia. Duration of CBIs was short-term (median 3 years; range 0.2-21.0 years), delivered mostly by health departments and local governments. Median annual funding had more than doubled since the 2010 survey, but average staffing had not increased. CBIs used at least two strategy types, with a preference for individual behaviour change strategies. Targeting children was less common (31%) compared with the 2010 survey (57%). Logic models and theory were used in planning, but there was low use of research evidence and existing prevention frameworks. Nearly, all CBIs had an evaluation component (12% of budget), but dissemination was limited. This survey provides information on the scope and varied quality of the current obesity prevention investment in Australia. To boost the quality and effectiveness of CBIs, further support systems may be required to ensure that organizations adopt upstream, evidence-informed approaches; and integrate CBIs into systems, policies and environments.


Effects of bisoprolol in combination with trimetazidine on the treatment of heart failure and concomitant chronic obstructive pulmonary disease.
To evaluate the effects of bisoprolol combined with trimetazidine on the treatment of heart failure patients having concomitant chronic obstructive pulmonary disease (COPD); in comparison with control group treated with standard therapy only. A total of 120 heart failure patients having concomitant COPD were selected and randomly divided into a control group and a treatment group according to different treatment methods (n=60). The control group was given continuous low flow oxygen inhalation and inotropic agents, and their cardiac stress was also reduced. The treatment group was treated with bisoprolol fumarate and trimetazidine in addition to treatment for COPD. For all patients, blood gas analysis and parameters reflecting cardiac function were measured respectively before and after treatment. The respiratory symptoms (cough, sputum, polypnea, gasp, dyspnea), limitation of motion (daily life, household duties, entertainment, sports), disease impacts (social contact, emotion, anxiety) and St. George's Respiratory Questionnaire (SGRQ) total scores were observed using SGRQ. The oxygen partial pressure (PaO2) and partial pressure of carbon dioxide (PaCO2) of the treatment group after treatment were significantly different from those before treatment. After treatment, peak E, E/A and IVEF were increased by 41%, 44% and 16% respectively, but peak A, LVPWT/mm and IVST/mm were significantly reduced. The differences in the respiratory symptoms, limitation of motion, disease impacts and SGRQ total scores were statistically significant compared with those before treatment (P<0.05) and those of the control group (P<0.05). Combining bisoprolol with trimetazidine in the treatment of heart failure complicating COPD can effectively improve blood gas indices, left ventricular systolic and diastolic functions and the quality of life, thereby alleviating clinical symptoms.


Characterizing standard genetic parts and establishing common principles for engineering legume and cereal roots.
Plant synthetic biology and cereal engineering depend on the controlled expression of transgenes of interest. Most engineering in plant species to date has relied heavily on the use of a few, well-established constitutive promoters to achieve high levels of expression; however, the levels of transgene expression can also be influenced by the use of codon optimization, intron-mediated enhancement and varying terminator sequences. Most of these alternative approaches for regulating transgene expression have only been tested in small-scale experiments, typically testing a single gene of interest. It is therefore difficult to interpret the relative importance of these approaches and to design engineering strategies that are likely to succeed in different plant species, particularly if engineering multigenic traits where the expression of each transgene needs to be precisely regulated. Here, we present data on the characterization of 46 promoters and 10 terminators in Medicago truncatula, Lotus japonicus, Nicotiana benthamiana and Hordeum vulgare, as well as the effects of codon optimization and intron-mediated enhancement on the expression of two transgenes in H. vulgare. We have identified a core set of promoters and terminators of relevance to researchers engineering novel traits in plant roots. In addition, we have shown that combining codon optimization and intron-mediated enhancement increases transgene expression and protein levels in barley. Based on our study, we recommend a core set of promoters and terminators for broad use and also propose a general set of principles and guidelines for those engineering cereal species.


Analysis of the binding of hepatitis C virus genotype 1a and 1b E2 glycoproteins to peripheral blood mononuclear cell subsets.
Hepatitis C virus (HCV) binding to hepatocytes is thought to be mediated via interaction of the E2 glycoprotein with (co-)receptors including CD81 and scavenger receptor class B type I (SR-BI). Here, the expression of CD81 and SR-BI was analysed on peripheral blood mononuclear cell (PBMC) subsets, and the binding of genotype 1 soluble truncated E2 (sE2) proteins to these cells was investigated. All PBMC subsets expressed CD81, although at varying levels. In contrast, SR-BI was only detected on monocytes and dendritic cells (DCs). The genotype 1a H77c sE2 protein showed higher PBMC binding than other genotype 1a/b sE2s. H77c sE2 binding to different PBMC subsets largely paralleled their level of CD81 expression, and could be inhibited by blocking E2-CD81 interaction. However, those PBMC subsets reported to be infected by HCV in vivo (monocytes, DCs and B cells) also exhibited residual, CD81-independent binding, indicating roles for SR-BI/other receptor(s) in mediating haematopoietic cell infection.


Pulsatile tinnitus associated with a laterally placed sigmoid sinus.
We describe a case of subjective pulsatile tinnitus associated with a laterally placed sigmoid sinus. CT showed an enhancing eroding through the medial wall of the right mastoid. Two-dimensional time-of-flight MR angiography and conventional cerebral angiography revealed the tortuous and laterally deviated sinus.


Selectivity of face distortion aftereffects for differences in expression or gender.
The perceived configuration of a face can be strongly biased by prior adaptation to a face with a distorted configuration. These aftereffects have been found to be weaker when the adapt and test faces differ along a number of dimensions. We asked whether the adaptation shows more transfer between faces that share a common identity, by comparing the strength of aftereffects when the adapt and test faces differed either in expression (a configural change in the same face identity) or gender (a configural change between identities). Observers adapted to expanded or contracted images of either male or female faces with either happy or fearful expressions, and then judged the perceived configuration in either the same faces or faces with a different gender and/or expression. The adaptation included exposure to a single face (e.g., expanded happy) or to alternated faces where the distortion was contingent on the attribute (e.g., expanded happy versus contracted fearful). In all cases the aftereffects showed strong transfer and thus only weak selectivity. However, selectivity was equal or stronger for the change in expression than gender. Our results thus suggest that the distortion aftereffects between faces can be weakly modulated by both variant and invariant attributes of the face.


Thymoma with pseudosarcomatous stroma.
Thymoma with psuedosarcomatous stroma is a recently described, rare variant of thymomas that are characterized by having a biphasic histologic pattern which consists of both an epithelial and a spindle cell stromal component. So far only 11 cases having similar histologic findings have been reported worldwide. At this time we report a case of this rare variant of thymoma which occurred in a 53-year-old Korean man. This previously healthy patient presented with coughing and an anterior mediastinal mass was then detected radiographically. Mediastinal exploration revealed a 9 x 8 x 8 cm-sized well- encapsulated, ovoid, cystic mass. Histological examination showed a biphasic neoplasm composed of anastomosing nests of epithelial cells and somewhat cellular stromal spindle cells that had advanced degenerative changes. Immunohistochemical staining using the antibodies for cytokeratins, EMA, e-cadherin, and p75NGFR showed a strong expression of these markers in the epithelial component but no expression in the spindle stromal cells. The epithelial tumor cells showed no reactivity to CD5 and L26 and a high proportion of the infiltrated lymphocytes were the cortical type that expressed CD99 and terminal deoxynucleotidyl transferase. Ultrastructural examinations revealed tonofilaments in the spindle cells. Follow up has been done for 5 years after the surgical excision and the patient has been free of disease during that period. Similar to previous reports, this patient had a benign clinical course that was unassociated with myasthenia gravis which appears to be a characteristic of this histologic variant of thymoma. However, our case also showed advanced degenerative features and we could demonstrate ultrastructural evidence of epithelial differentiation in the stromal spindle cells that were not mentioned in the previously reported cases. Based on the results of our studies, we suggest this entity is a distinct type of organotypic thymoma that shows cortical differentiation and abundant cellular stroma.


Isolation of Babesia divergens from carrier cattle blood using in vitro culture.
Babesia divergens, the main causative agent of bovine babesiosis in Western Europe, was isolated from naturally infected cattle. Ninety-six blood samples were examined by means of an in vitro culture technique in sheep erythrocytes: 19 of them were collected from animals in the acute phase of the disease with visible parasitemia on blood smears, while the 77 remaining animals showed no microscopically detectable parasites. B. divergens was cultured from the 19 first blood samples as well as from 31 samples collected from asymptomatic animals. The time period before parasites could be detected in the culture varied in the latter samples from 6 to 20 days. The effects of sampling condition (anticoagulant used) and storage length were tested. A good correlation was obtained between immunofluorescent antibody test and culture, with identical results (positive or negative) for 89.6% of the samples collected from asymptomatic animals. The sensitivity of the in vitro culture method was determined and was about 10 parasites/mL of whole blood from three independent experiments performed with three different isolates, confirming its suitability to detect and culture diverse B. divergens isolates from carrier cattle. The parasites could indeed be isolated 9 months after the acute babesiosis phase in the blood of naturally infected animals. The 50 isolates collected in this study were successfully subcultured, cryopreserved and resuscitated using the same culture medium. The in vitro isolation of B. divergens from asymptomatic carrier cattle was achieved and will allow the analysis of parasite diversity within cattle herds.


Direct involvement of tumor necrosis factor-α in the regulation of glucose uptake in rainbow trout muscle cells.
The proinflammatory cytokine TNF-α is known to have a direct action on skeletal muscle in mammals. However, little is known regarding the potential effects of cytokines on nonimmune tissues, particularly in skeletal muscle, in fish. The aim of this study was to investigate the effects of recombinant trout TNF-α (rtTNF-α) on skeletal muscle carbohydrate metabolism in rainbow trout (Oncorhynchus mykiss). We used a primary cell culture of muscle cells from rainbow trout to show that rtTNF-α stimulates glucose uptake in myoblasts and myotubes at concentrations that do not affect the viability of the cells, requiring de novo protein synthesis as shown by the impairment of rtTNF-α-stimulated glucose uptake by cycloheximide. With the use of specific inhibitors, we show that rtTNF-α-stimulated glucose uptake is mediated by the p38MAPK, NF-κB, and JNK pathways. Additionally, we provide evidence that the stimulatory effects of rtTNF-α on glucose uptake in trout skeletal muscle cells may be caused, at least in part, by an increase in the amount of GLUT4 at the plasma membrane. Incubation of trout muscle cells with conditioned medium from LPS-stimulated trout macrophages, enriched in TNF-α, increased glucose uptake. Our results indicate that recombinant, as well as native trout TNF-α, directly stimulates glucose uptake in trout muscle cells and provide evidence, for the first time in nonmammalian vertebrates, for a potential regulatory role of TNF-α in skeletal muscle metabolism.


Long range interactions between oriented texture elements.
Long range interactions between texture elements (short, oriented line segments) were examined. Specifically, we studied the influence of a background array of texture elements on the detectability of a target element (separated from the background by an intermediate textured region) using textures like those of Caputo (Vis. Res. 1996, 36, 2815-2826). We found that, in general, when the background elements were oriented orthogonally to the target element, detection of the target element was better than when the background elements had the same orientation as the target element. We discuss these interactions in terms of inhibitory and excitatory connections between orientation and spatial frequency selective linear filters (e.g. filters which mimic V1 simple cells) which would respond to the individual texture elements.


[Nudges and the pandemic: An analysis from economics and behavioural law. SESPAS Report 2022].
Behavioural economics (a combination of economics and psychology) provides keys to understand decisions made by politicians and citizens along the COVID-19 pandemic through the so-called cognitive biases. These biases can be offset by implementing behavioural interventions named "nudges" in order to promote responsible behaviours in the "new normality". This paper analyses, from a behavioural economics perspective, past, present and future of behavioural aspects surrounding the pandemic. Besides, this paper proposes different ways to formalize nudges according to law, which needs the fulfilment of three minimum requirements, namely: transparency, non-arbitrariness and efficiency. Furthermore, it is also suggested that protocols and contingency plans are set up to face future pandemics, in which both soft (nudge-type) interventions and hard legal regulations play different roles but complementary ones. Nudges can be implemented in a fast and less coercive way, so they are particularly suitable for changing mild misbehaviour, reserving legal sanctions for the more serious ones.


Xanthohumol induces apoptosis in human malignant glioblastoma cells by increasing reactive oxygen species and activating MAPK pathways.
The effect of the biologically active prenylated chalcone and potential anticancer agent xanthohumol (1) has been investigated on apoptosis of the T98G human malignant glioblastoma cell line. Compound 1 decreased the viability of T98G cells by induction of apoptosis in a time- and concentration-dependent manner. Apoptosis induced by 1 was associated with activation of caspase-3, caspase-9, and PARP cleavage and was mediated by the mitochondrial pathway, as exemplified by mitochondrial depolarization, cytochrome c release, and downregulation of the antiapoptotic Bcl-2 protein. Xanthohumol induced intracellular reactive oxygen species (ROS), an effect that was reduced by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC). Intracellular ROS production appeared essential for the activation of the mitochondrial pathway and induction of apoptosis after exposure to 1. Oxidative stress due to treatment with 1 was associated with MAPK activation, as determined by ERK1/2 and p38 phosphorylation. Phosphorylation of ERK1/2 and p38 was attenuated using NAC to inhibit ROS production. After treatment with 1, ROS provided a specific environment that resulted in MAPK-induced cell death, with this effect reduced by the ERK1/2 specific inhibitor PD98059 and partially inhibited by the p38 inhibitor SB203580. These findings suggest that xanthohumol (1) is a potential chemotherapeutic agent for the treatment of glioblastoma multiforme.


Lichen myxedematosus serum stimulates human skin fibroblast proliferation.
Serum from patients with lichen myxedematosus, when added to exponentially growing normal human skin fibroblasts, stimulates DNA synthesis and cell proliferation. The degree of response in vitro is correlated with the extent of the disease in vivo and is specific for fibroblasts. The results suggest that there is a systemic factor (or factors) which may play a role in the etiology of diseases affecting the connective tissue.