Molecular epidemiology of malaria prevalence and parasitaemia in a wild bird population.
Avian malaria (Plasmodium spp.) and other blood parasitic infections of birds constitute increasingly popular model systems in ecological and evolutionary host-parasite studies. Field studies of these parasites commonly use two traits in hypothesis testing: infection status (or prevalence at the population level) and parasitaemia, yet the causes of variation in these traits remain poorly understood. Here, we use quantitative PCR to investigate fine-scale environmental and host predictors of malaria infection status and parasitaemia in a large 4-year data set from a well-characterized population of blue tits (Cyanistes caeruleus). We also examine the temporal dynamics of both traits within individuals. Both infection status and parasitaemia showed marked temporal and spatial variation within this population. However, spatiotemporal patterns of prevalence and parasitaemia were non-parallel, suggesting that different biological processes underpin variation in these two traits at this scale. Infection probability and parasitaemia both increased with host age, and parasitaemia was higher in individuals investing more in reproduction (those with larger clutch sizes). Several local environmental characteristics predicted parasitaemia, including food availability, altitude, and distance from the woodland edge. Although infection status and parasitaemia were somewhat repeatable within individuals, infections were clearly dynamic: patent infections frequently disappeared from the bloodstream, with up to 26% being lost between years, and parasitaemia also fluctuated within individuals across years in a pattern that mirrored annual population-level changes. Overall, these findings highlight the ecological complexity of avian malaria infections in natural populations, while providing valuable insight into the fundamental biology of this system that will increase its utility as a model host-parasite system.


Safety of early performance of the six-minute walk test following acute myocardial infarction: a cross-sectional study.
The six-minute walk test (6MWT) is a simple, low cost, reliable, and valid method for evaluating the functional capacity of cardiac patients. However, its early use and safety following acute myocardial infarction (AMI) is recent and has been little investigated. To evaluate and to compare the safety and the cardiac behavior of early performance of the 6MWT in patients following uncomplicated AMI up to 4 days or more than 4 days after the event. Following discharge from the Coronary Care Unit, 152 stable asymptomatic patients diagnosed with uncomplicated AMI performed the 6MWT. During the test, in addition to the distance walked, heart rate (HR), blood pressure (BP), and adverse events were also recorded. Electrocardiography was recorded using a Holter monitor in 105 patients. Patients were allocated considering two groups according to the number of days since AMI: Up to 4 Days Group and After 4 Days Group. All patients completed the 6MWT, 66 in the Up to 4 Days Group and 86 in the After 4 Days Group. The walking distance was similar in both groups (85% of the predicted value), as well as the physiological responses (increase in systolic BP and HR), reaching 63% (median) of maximum HR. Only 3.9% of patients had major complications (angina, drop in BP, or ventricular tachycardia), with no difference between the groups. None of the complications regarded as severe led to truly significant complications or death. The 6MWT was proven to be safe and feasible for early functional evaluation following uncomplicated AMI.


Effect of six weeks aerobic training upon blood trace metals levels.
This study was carried out to investigate the effects of 6-week aerobic exercise program upon blood Zn and Cu levels. There were 12 male university students with an average age of 21.67+/-0.89 years and no regular training habits participated in the study. The participants were subjected three days a week 1 hour a day continuous running program on treadmill with an intensity of 60-70% for a period of six weeks. They were fed with zinc and copper free diet throughout the study and it was made sure that they were not using copper or zinc containing vitamin tablets. The difference between the pre and post study period were found to be statistically significant as regards to both resting and maximal loading conditions (p<0.01). The pre and post training maxVO2 values were also found to be positively correlated with the copper and zinc levels in blood. Both the copper and zinc blood levels were found decreased after the training period p<0.05.


Effects of tobacco dose and length of exposure on delayed neurological deterioration and overall clinical outcome after aneurysmal subarachnoid hemorrhage.
The association between smoking and intracranial aneurysms is now well recognized. However, the relationship between tobacco use and outcome after aneurysmal subarachnoid hemorrhage (SAH) is not as well understood and published results are contradictory. The purpose of this study is to examine the degree to which the amount of tobacco exposure/dose impacts delayed neurological deterioration and overall clinical outcome after aneurysmal SAH. We reviewed our retrospective database of patients with aneurysmal SAH. We assessed the impact of four independent tobacco variables: smoker (ever smoked), current smoker (actively smoking within the past yr and with at least a 10 pack per yr history of smoking), long-term smoker (at least a 20 pack per yr history), and salient (combination of current and long-term) smoker as well as tobacco dose (categorized according to number of packs per yr) on two outcome variables, delayed neurological deterioration and dichotomized Glasgow Outcome Scale score. Covariates included in the analysis were age, sex, Hunt and Hess grade, Fisher grade, and medical comorbidities. Stepwise elimination with logistic regression was used to arrive at a final multivariate model for each outcome and independent tobacco variable in the presence of covariates. A total of 320 patients were analyzed. As expected, Hunt and Hess grade was a significant predictor of both delayed neurological deterioration and clinical outcome. Tobacco use (smoker variable) showed an independent association with the development of delayed neurological deterioration (P = 0.0409; odds ratio, 1.78; 95% confidence interval, 1.02-3.08). In addition, patients who were long-term or current smokers (salient smoker variable) showed a trend toward a slightly stronger association with the occurrence of delayed neurological deterioration (P = 0.0229; odds ratio, 1.85; 95% confidence interval, 1.09-3.14). No tobacco use variable was associated with clinical outcome (Glasgow Outcome Scale) in the multivariate analysis. The duration and timing of tobacco use, rather than the dose of tobacco per se, seem to be risk factors for delayed neurological deterioration after aneurysmal SAH. Although we did not find an association between tobacco use and overall clinical outcome after aneurysmal SAH, these results suggest that the distribution of various patterns of tobacco use within a given data set may influence the overall results.


Diversity patterns, ecological associations and future of research on Costa Rican myxomycetes.
The most active research period on myxomycetes in Costa Rica has taken place in the last three decades. During this time, most of the collections have been carried out and most of the scientific articles have been produced. However, the lack of standard protocols and systematic planning across the country generated a need to conduct an analysis of myxomycete records to define future lines of work. A compilation, cleaning, standardisation and analysis of information associated with a database of more than 7800 records that comprised 242 species of myxomycetes reported in Costa Rica during the last 110 years, was carried out. An interpretation of data with a conservation approach that integrated elements of data-mining and geographical information systems was conducted. Results showed that myxomycetes has been comparatively well studied in Costa Rica in relation to other regional or tropical countries. However, survey effort has been unequal within the territory, leaving some interesting areas or substrates understudied. The absence of long-term goals to study this country and Mesoamerica has limited the potential that the analysed data can have within the context of conservation. This could be the next logical step in the study of this group of microorganisms in that country.


Comparison of single vs double noncompression miniplates in the management of subcondylar fracture of the mandible.
The purpose of this study was to compare the functions of the condyle and complications after fixation of a subcondylar fracture of the mandible with two noncompression miniplates and a single non-compression miniplate. A total of 30 patients who required open reduction of a subcondylar fracture of mandible were selected for the study. The patients were randomly divided into two groups of 15 each. Group I comprised of patients treated with a single miniplate and Group II were treated with two noncompression miniplates. The patients were assessed for malocclusion, lateral deviation on opening, infection, plate removal, facial nerve function, the time taken in the surgery, and cost of implants used, in both the groups. All the parameters were compared statistically using the chi square test. Out of 30 patients, inadequate reduction was noticed in one patient in Group I. Screw loosening occurred in two cases; both the cases were stabilized with a single miniplate. Screw loosening was always associated with chronic infection. In these cases, hardware removal was performed. Plate bending was observed in one case that was stabilized with a single miniplate. Malocclusion and lateral deviation occurred in this case. When two miniplate were used, no plate bending or screw loosening was observed. Malocclusion was observed in Group II. Two plates for subcondylar fractures represent the best solution to obtain stable osteosynthesis in comparison to a single miniplate.


Under cover at pre-angiosperm times: a cloaked phasmatodean insect from the Early Cretaceous Jehol biota.
Fossil species that can be conclusively identified as stem-relatives of stick- and leaf-insects (Phasmatodea) are extremely rare, especially for the Mesozoic era. This dearth in the paleontological record makes assessments on the origin and age of the group problematic and impedes investigations of evolutionary key aspects, such as wing development, sexual size dimorphism and plant mimicry. A new fossil insect species, Cretophasmomima melanogramma Wang, Béthoux and Ren sp. nov., is described on the basis of one female and two male specimens recovered from the Yixian Formation (Early Cretaceous, ca. 126±4 mya; Inner Mongolia, NE China; known as 'Jehol biota'). The occurrence of a female abdominal operculum and of a characteristic 'shoulder pad' in the forewing allows for the interpretation of a true stem-Phasmatodea. In contrast to the situation in extant forms, sexual size dimorphism is only weakly female-biased in this species. The peculiar wing coloration, viz. dark longitudinal veins, suggests that the leaf-shaped plant organ from the contemporaneous 'gymnosperm' Membranifolia admirabilis was used as model for crypsis. As early as in the Early Cretaceous, some stem-Phasmatodea achieved effective leaf mimicry, although additional refinements characteristic of recent forms, such as curved fore femora, were still lacking. The diversification of small-sized arboreal insectivore birds and mammals might have triggered the acquisition of such primary defenses.


An object-oriented simulator for 3D digital breast tomosynthesis imaging system.
Digital breast tomosynthesis (DBT) is an innovative imaging modality that provides 3D reconstructed images of breast to detect the breast cancer. Projections obtained with an X-ray source moving in a limited angle interval are used to reconstruct 3D image of breast. Several reconstruction algorithms are available for DBT imaging. Filtered back projection algorithm has traditionally been used to reconstruct images from projections. Iterative reconstruction algorithms such as algebraic reconstruction technique (ART) were later developed. Recently, compressed sensing based methods have been proposed in tomosynthesis imaging problem. We have developed an object-oriented simulator for 3D digital breast tomosynthesis (DBT) imaging system using C++ programming language. The simulator is capable of implementing different iterative and compressed sensing based reconstruction methods on 3D digital tomosynthesis data sets and phantom models. A user friendly graphical user interface (GUI) helps users to select and run the desired methods on the designed phantom models or real data sets. The simulator has been tested on a phantom study that simulates breast tomosynthesis imaging problem. Results obtained with various methods including algebraic reconstruction technique (ART) and total variation regularized reconstruction techniques (ART+TV) are presented. Reconstruction results of the methods are compared both visually and quantitatively by evaluating performances of the methods using mean structural similarity (MSSIM) values.


Structural complexities in the active layers of organic electronics.
The field of organic electronics has progressed rapidly in recent years. However, understanding the direct structure-function relationships between the morphology in electrically active layers and the performance of devices composed of these materials has proven difficult. The morphology of active layers in organic electronics is inherently complex, with heterogeneities existing across multiple length scales, from subnanometer to micron and millimeter range. A major challenge still facing the organic electronics community is understanding how the morphology across all of the length scales in active layers collectively determines the device performance of organic electronics. In this review we highlight experiments that have contributed to the elucidation of structure-function relationships in organic electronics and also point to areas in which knowledge of such relationships is still lacking. Such knowledge will lead to the ability to select active materials on the basis of their inherent properties for the fabrication of devices with prespecified characteristics.


Biochemical characterization of a gamma interferon-inducible cytokine (IP-10).
An IFN-gamma-inducible protein, IP-10, has previously been described to belong to a gene family of chemotactic and mitogenic proteins, associated with inflammation and proliferation. Biochemical characterization of this predicted protein has been pursued through the development of polyclonal monospecific antisera to recombinant protein and synthetic peptides. These reagents establish that the IP-10 protein is secreted from a variety of cells (endothelial, monocyte, fibroblast, and keratinocyte) in response to IFN-gamma. Posttranslational processing occurs in the biosynthesis of this protein, resulting in a 6-7-kD species, which may reflect COOH-terminal cleavage. Pulse-chase studies indicate that this processing is a rapid event in the primary cell lines studied, completed in the 30-min labeling period. A model is presented for the processing and secondary structure of this protein. In an accompanying study, Kaplan, et al. using these antisera, demonstrate that the IP-10 protein is associated, in vivo, with a delayed-type hypersensitivity response.


Novel competitors shape species' responses to climate change.
Understanding how species respond to climate change is critical for forecasting the future dynamics and distribution of pests, diseases and biological diversity. Although ecologists have long acknowledged species' direct physiological and demographic responses to climate, more recent work suggests that these direct responses can be overwhelmed by indirect effects mediated via other interacting community members. Theory suggests that some of the most dramatic impacts of community change will probably arise through the assembly of novel species combinations after asynchronous migrations with climate. Empirical tests of this prediction are rare, as existing work focuses on the effects of changing interactions between competitors that co-occur today. To explore how species' responses to climate warming depend on how their competitors migrate to track climate, we transplanted alpine plant species and intact plant communities along a climate gradient in the Swiss Alps. Here we show that when alpine plants were transplanted to warmer climates to simulate a migration failure, their performance was strongly reduced by novel competitors that could migrate upwards from lower elevation; these effects generally exceeded the impact of warming on competition with current competitors. In contrast, when we grew the focal plants under their current climate to simulate climate tracking, a shift in the competitive environment to novel high-elevation competitors had little to no effect. This asymmetry in the importance of changing competitor identity at the leading versus trailing range edges is best explained by the degree of functional similarity between current and novel competitors. We conclude that accounting for novel competitive interactions may be essential to predict species' responses to climate change accurately.


Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: does heterogeneity of estimates relate to study design?
The INSIG2 rs7566605 polymorphism was identified for obesity (BMI> or =30 kg/m(2)) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status ('healthy population', HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I(2) measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I(2) measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI> or =32.5, 35.0, 37.5, 40.0 kg/m(2) versus BMI<25 kg/m(2)) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far.


Salmonella enterica serovar Typhi H58 clone has been endemic in Zimbabwe from 2012 to 2019.
Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control. To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics. A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis. A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, β-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (126.96.36.199), with a maximum pair-wise distance of 22 SNPs. This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi 188.8.131.52 (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance.


Aquatic Insects in Eastern Australia: A Window on Ecology and Evolution of Dispersal in Streams.
Studies of connectivity of natural populations are often conducted at different timescales. Studies that focus on contemporary timescales ask questions about dispersal abilities and dispersal behavior of their study species. In contrast, studies conducted at historical timescales are usually more focused on evolutionary or biogeographic questions. In this paper we present a synthesis of connectivity studies that have addressed both these timescales in Australian Trichoptera and Ephemeroptera. We conclude that: (1) For both groups, the major mechanism of dispersal is by adult flight, with larval drift playing a very minor role and with unusual patterns of genetic structure at fine scales explained by the "patchy recruitment hypothesis"; (2) There is some evidence presented to suggest that at slightly larger spatial scales (~100 km) caddisflies may be slightly more connected than mayflies; (3) Examinations of three species at historical timescales showed that, in southeast Queensland Australia, despite there being no significant glaciation during the Pleistocene, there are clear impacts of Pleistocene climate changes on their genetic structure; and (4) The use of mitochondrial DNA sequence data has uncovered a number of cryptic species complexes in both trichopterans and ephemeropterans. We conclude with a number of suggestions for further work.


A Hypergraph-Based Reduction for Higher-Order Binary Markov Random Fields.
Higher-order Markov Random Fields, which can capture important properties of natural images, have become increasingly important in computer vision. While graph cuts work well for first-order MRF's, until recently they have rarely been effective for higher-order MRF's. Ishikawa's graph cut technique [1], [2] shows great promise for many higher-order MRF's. His method transforms an arbitrary higher-order MRF with binary labels into a first-order one with the same minima. If all the terms are submodular the exact solution can be easily found; otherwise, pseudoboolean optimization techniques can produce an optimal labeling for a subset of the variables. We present a new transformation with better performance than [1], [2], both theoretically and experimentally. While [1], [2] transforms each higher-order term independently, we use the underlying hypergraph structure of the MRF to transform a group of terms at once. For n binary variables, each of which appears in terms with k other variables, at worst we produce n non-submodular terms, while [1], [2] produces O(nk). We identify a local completeness property under which our method perform even better, and show that under certain assumptions several important vision problems (including common variants of fusion moves) have this property. We show experimentally that our method produces smaller weight of non-submodular edges, and that this metric is directly related to the effectiveness of QPBO [3]. Running on the same field of experts dataset used in [1], [2] we optimally label significantly more variables (96 versus 80 percent) and converge more rapidly to a lower energy. Preliminary experiments suggest that some other higher-order MRF's used in stereo [4] and segmentation [5] are also locally complete and would thus benefit from our work.


Sustainable energy, economic growth and public health.
Dramatic economic growth over the last 50 years has been accompanied by widening inequalities world-wide in wealth and energy consumption, diminished life expectancy in some countries, and deteriorating indices of environmental sustainability including loss of bio-diversity. Raised output of carbon dioxide (CO2) and other greenhouse gases due to increased economic and industrial activity is causing progressive climate change, leading in turn to direct and indirect adverse effects on health. Emissions of greenhouse gases can be lowered by increased use of renewable energy sources, for example, wind power in the United Kingdom (UK), greater energy efficiency and other measures to promote sustainability. The experience of some developing countries shows that favourable indicators of health and development can accompany a low output of greenhouse gases. It is unclear whether contemporary political and social systems can deliver improved human development without increased use of fossil fuels and other resources.


Percutaneous Cava Stenting in a Dog with Symptomatic Azygos Continuation of the Caudal Vena Cava.
This report describes the successful placement of a nitinol stent within the azygos continuation of the caudal vena cava in a 2-year-old, neutered female, English Bulldog with clinical and imaging signs related to venous return chronic obstruction, renal venous thrombi, and chronic renal insufficiency. This noninvasive, interventional radiology procedure was safe and clinically effective for the patient. The clinical signs were rapidly eliminated, and three years later, the patient is still in good clinical condition, with normal renal function. Venous stenting appears to be a useful, new, minimally invasive treatment option for symptomatic cavo-azygos vascular connection.


Implants for the ageing population.
Dental implant treatment has established benefits over traditional alternatives. Age-related changes in systemic and oral health in conjunction with social, economic and resource considerations often introduce complexities into dental implant treatment of ageing patients. When time, opportunity, discomfort and maintenance costs are coupled with cost-benefit and quality of life predictions, otherwise simple treatment decisions can become more difficult. Implants for different types of prostheses in both arches and the different types of prostheses themselves present a variety of treatment challenges, risks, benefits and maintenance requirements. This narrative review discusses selective literature pertinent to the provision of dental implant treatment in the ageing population.


Manikin Human-Patient Simulator Training.
Human-patient simulators (HPSs) may help enhance medical education. Manikin HPS devices respond to common field medical interventions, such as cricothyroidotomy, and have realistic feedback features, such as respirations and pulses. This study surveys Special Operations Medics for evaluations of HPS features. Of 518 subjects, 376 completed testing and surveys with valid responses. A total of 102 variables were divided into three categories-general characteristics, procedures, and injuries-and assessed on a fivepoint Likert scale. The Student t test was used to analyze data together and as separate groups against each other and against an aggregated mean. Features that received high scores (i.e., higher than 4.5/5) corresponded closely with pillars of the Tactical Combat Casualty Care (TCCC) curriculum, basic life support, and realism. US Army Special Operations Command and US Special Operations Command Medics have overall high confidence in manikin HPS devices and specifically in those that align with TCCC training and lifesaving procedures. The skills most valued coincide with difficult-to-practice measures, such as cricothyroidotomy and wound packing. Features such as prerecorded sounds, sex, automated movements, skin color, defibrillation, bowel sounds, and electrocardiogram are rated lower. These evaluations may guide future development or procurement of manikin HPS devices.


How I Do It: The pudendal nerve block for pediatric ambulatory urologic surgery.
Regional analgesia is an important adjunct for perioperative pain management in the setting of pediatric penile surgeries. Caudal epidural analgesia (CEA) is the most common analgesic technique performed, but it has limitations and associated morbidity. The pudendal nerve block (PNB) is an effective alternative to CEA with a lower risk profile; in prior examination of the approach, PNB has been demonstrated to have similar postoperative pain control outcomes. We describe our technique and highlight observations made as we have transitioned from CEA to PNB for many patients.


Neurologic phenotypes associated with COL4A1/2 mutations: Expanding the spectrum of disease.
To characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype-phenotype correlation. We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations. Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI colocalized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed nonspecific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of 15 pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype-phenotype correlation did not emerge. COL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, while for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall.


Not on my team: Medial prefrontal cortex responses to ingroup fusion and unfair monetary divisions.
People are highly attuned to fairness, with people willingly suffering personal costs to prevent others benefitting from unfair acts. Are fairness judgments influenced by group alignments? A new theory posits that we favor ingroups and denigrate members of rival outgroups when our personal identity is fused to a group. Although the mPFC has been separately implicated in group membership and fairness processing, it is unclear whether group alignments affect medial prefrontal cortex (mPFC) activity in response to fairness. Here, we examine the contribution of different regions of the mPFC to processing from ingroup and outgroup members and test whether its response differs depending on how fused we are to an ingroup. Subjects performed rounds of the Ultimatum Game, being offered fair or unfair divisions of money from supporters of the same soccer team (ingroup), the fiercest rival (outgroup) or neutral individuals whilst undergoing functional Magnetic Resonance Imaging (fMRI). Strikingly, people willingly suffered personal costs to prevent outgroup members benefitting from both unfair and fair offers. Activity across dorsal and ventral (VMPFC) portions of the mPFC reflected an interaction between fairness and group membership. VMPFC activity in particular was consistent with it coding one's fusion to a group, with the fairness by group membership interaction correlating with the extent that the responder's identity was fused to the ingroup. The influence of fusion on social behavior therefore seems to be linked to processing in the VMPFC.


Reduction of intimal hyperplasia in injured rat arteries promoted by catheter balloons coated with polyelectrolyte multilayers that contain plasmid DNA encoding PKCδ.
New therapeutic approaches that eliminate or reduce the occurrence of intimal hyperplasia following balloon angioplasty could improve the efficacy of vascular interventions and improve the quality of life of patients suffering from vascular diseases. Here, we report that treatment of arteries using catheter balloons coated with thin polyelectrolyte-based films ('polyelectrolyte multilayers', PEMs) can substantially reduce intimal hyperplasia in an in vivo rat model of vascular injury. We used a layer-by-layer (LbL) process to coat the surfaces of inflatable catheter balloons with PEMs composed of nanolayers of a cationic poly(β-amino ester) (polymer 1) and plasmid DNA (pPKCδ) encoding the δ isoform of protein kinase C (PKCδ), a regulator of apoptosis and other cell processes that has been demonstrated to reduce intimal hyperplasia in injured arterial tissue when administered via perfusion using viral vectors. Insertion of balloons coated with polymer 1/pPKCδ multilayers into injured arteries for 20 min resulted in local transfer of DNA and elevated levels of PKCδ expression in the media of treated tissue three days after delivery. IFC and IHC analysis revealed these levels of expression to promote downstream cellular processes associated with up-regulation of apoptosis. Analysis of arterial tissue 14 days after treatment revealed polymer 1/pPKCδ-coated balloons to reduce the occurrence of intimal hyperplasia by ~60% compared to balloons coated with films containing empty plasmid vectors. Our results demonstrate the potential therapeutic value of this nanotechnology-based approach to local gene delivery in the clinically important context of balloon-mediated vascular interventions. These PEM-based methods could also prove useful for other in vivo applications that require short-term, surface-mediated transfer of plasmid DNA.


SMN-primed ribosomes modulate the translation of transcripts related to spinal muscular atrophy.
The contribution of ribosome heterogeneity and ribosome-associated proteins to the molecular control of proteomes in health and disease remains unclear. Here, we demonstrate that survival motor neuron (SMN) protein-the loss of which causes the neuromuscular disease spinal muscular atrophy (SMA)-binds to ribosomes and that this interaction is tissue-dependent. SMN-primed ribosomes are preferentially positioned within the first five codons of a set of mRNAs that are enriched for translational enhancer sequences in the 5' untranslated region (UTR) and rare codons at the beginning of their coding sequence. These SMN-specific mRNAs are associated with neurogenesis, lipid metabolism, ubiquitination, chromatin regulation and translation. Loss of SMN induces ribosome depletion, especially at the beginning of the coding sequence of SMN-specific mRNAs, leading to impairment of proteins that are involved in motor neuron function and stability, including acetylcholinesterase. Thus, SMN plays a crucial role in the regulation of ribosome fluxes along mRNAs encoding proteins that are relevant to SMA pathogenesis.


Comparative in vitro evaluation of efficacy of mouthrinses against Streptococcus mutans, Lactobacilli and Candida albicans.
The present study was undertaken to compare the relative antimicrobial efficacy of two commercially available mouthrinses, Hexidine (0.12% chlorhexidine mouthrinse) and S-Flo (0.2% sodium fluoride), and a laboratory-manufactured propolis mouthrinse (10%) tincture with a dilution of 1:5 with water and their combinations against Streptococcus mutans, lactobacilli and Candida albicans. Unstimulated saliva samples were obtained from the patients using the spitting method and the isolates of Streptococcus mutans, Lactobacillus and Candida albicans were obtained. The agar diffusion method was used to evaluate the antimicrobial activity of these test solutions and their combinations. Hexidine (0.12% chlorhexidine gluconate mouthrinse) showed the best antimicrobial efficacy against all the tested microorganisms. The laboratory manufactured propolis mouthrinse showed an effective antimicrobial action only against Streptococcus mutans. The antimicrobial efficacy of propolis (P) against Streptococcus mutans was similar to that of chlorhexidine (CHX) and the combination of propolis with chlorhexidine (CHX+P). S-Flo mouthrinse (0.2% sodium fluoride) showed the least efficacy against Streptococcus mutans among all tested solutions, but had better efficacy than propolis against lactobacilli and Candida albicans. The antimicrobial efficacy of the combination of chlorhexidine and fluoride mouthrinse and the combination of chlorhexidine and propolis mouthrinse was less than chlorhexidine mouthwash alone. Among all the tested combinations, the combination of fluoride and propolis showed the least efficacy against all the tested microorganisms. The results of the study indicate that 0.12% chlorhexidine gluconate mouthrinse (Hexidine) has the best anti-microbial efficacy against all the tested microorganisms, with laboratory-manufactured propolis mouthrinse showing an equivalent efficacy against Streptococcus mutans only. No added advantage of using the tested mouthrinse combinations was observed.


Spatial filter and its application in three-dimensional single molecule localization microscopy.
Single molecule localization microscopy (SMLM) allows the imaging of cellular structures with resolutions five to ten times below the diffraction limit of optical microscopy. It was originally introduced as a two-dimensional technique based on the localization of single emitters as projection onto the x-y imaging plane. The determination of the axial position of a fluorescent emitter is only possible by additional information. Here we report a method (spatial filter SMLM (SFSMLM)) that allows to determine the axial positions of fluorescent molecules and nanoparticles on the nanometer scale by the usage of two spatial filters, which are placed in two otherwise identical emission detection channels. SFSMLM allows axial localization in a range of ca. 1.5 μm with a localization precision of 15 - 30 nm in axial direction. The technique was utilized for localizing and imaging small cellular structures - e.g. actin filaments, vesicles and mitochondria - in three dimensions.


A non-destructive technique for 3-D microstructural phenotypic characterisation of bones in genetically altered mice: preliminary data in growth hormone transgenic animals and normal controls.
A non-destructive, three-dimensional technique for microstructural phenotypic characterisation of skeletal elements in genetically altered mice is presented. Preliminary data in bovine growth-hormone transgenic animals and control littermates are shown. The technique is based on microcomputed tomography (microCT) and digital postprocessing and allows for a differential quantitative analysis of the cortical and trabecular bone compartments in the axial and peripheral skeleton. The distal femora and the first lumbar vertebral bodies of six animals were CT scanned in the axial plane with an isotropic resolution of 20 microm. The periostal surface and the marrow spaces were segmented fully automatically, and the trabecular and cortical compartments were separated interactively. After 3-D reconstruction, various regions of interest (diaphyseal, metaphyseal and epiphyseal) were selected for the analysis. The femora and vertebrae of the transgenic animals showed obvious differences in size, shape, and trabecular arrangement compared with the control animals. The total bone mass was increased by a factor of two to three, but the trabecular bone was increased much more (up to 12 times) than the cortical bone. The transgenic animals showed an increased ratio of trabecular vs cortical bone (0.90 to 1.27 vs 0.14 to 0.36 in the femoral diaphysis) and an elevated trabecular bone volume fraction (49% to 73% vs 18% to 43% in the femoral metaphysis). The mean 3-D cortical thickness was similar in the normal and transgenic animals (values between 93 microm and 232 microm in the dia- and metaphyses), but the minimal cortical thickness was lower in the transgenic animals (22 to 31 microm vs 54 microm to 110 microm in the diaphysis). The technique presented is suitable for phenotypic characterisation of bone structure in genetically altered mice.


Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner.
Cognitive dysfunction and reactive microglia are hallmarks of traumatic brain injury (TBI), yet whether these cells contribute to cognitive deficits and secondary inflammatory pathology remains poorly understood. Here, we show that removal of microglia from the mouse brain has little effect on the outcome of TBI, but inducing the turnover of these cells through either pharmacologic or genetic approaches can yield a neuroprotective microglial phenotype that profoundly aids recovery. The beneficial effects of these repopulating microglia are critically dependent on interleukin-6 (IL-6) trans-signaling via the soluble IL-6 receptor (IL-6R) and robustly support adult neurogenesis, specifically by augmenting the survival of newborn neurons that directly support cognitive function. We conclude that microglia in the mammalian brain can be manipulated to adopt a neuroprotective and pro-regenerative phenotype that can aid repair and alleviate the cognitive deficits arising from brain injury.


A Comprehensive Approach to Pouch Disorders.
Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with medically refractory ulcerative colitis (UC) or indeterminate colitis, UC with colonic dysplasia or neoplasia, and familial adenomatous polyposis. In general, patients experience good function outcomes and quality of life with an IPAA. Although pouchitis is the most well-recognized and frequent complication after IPAA, a number of additional inflammatory, postsurgical, structural, neoplastic, and functional complications may occur, resulting in pouch dysfunction. We herein provide a comprehensive review of pouch function and an approach to diagnosis and management of pouch complications.


Foraging, bioenergetic and predation constraints on diel vertical migration: field observations and modelling of reverse migration by young-of-the-year herring Clupea harengus.
Diel vertical migration (DVM) of young-of-the-year (YOY) herring Clupea harengus and one of their major predators, pikeperch Sander lucioperca, was examined using bottom-mounted hydroacoustics in Himmerfjärden, a brackish bay of the Baltic Sea, in summer. In contrast to previous studies on DVM of C. harengus aggregated across size and age classes, YOY C. harengus showed a reverse DVM trajectory, deeper at night and, on average, shallower during the day. This pattern was observed consistently on five acoustic sampling occasions in 3 years and was corroborated by two out of three trawl surveys. Large acoustic targets (target strength >-33 dB, probably piscivorous S. lucioperca >45 cm) showed a classic DVM trajectory, shallow at night and deeper during the day. Variability in YOY C. harengus vertical distribution peaked at dawn and dusk, and their vertical distribution at midday was distinctly bimodal. This reverse DVM pattern was consistent with bioenergetic model predictions for YOY C. harengus which have rapid gut evacuation rates and do not feed at night. Reverse DVM also resulted in low spatial overlap with predators.


Identifying, affirming, and building upon male strengths: the positive psychology/positive masculinity model of psychotherapy with boys and men.
The bulk of the extant literature on the psychology of boys, men and masculinity has been focused on the important challenges of: a) creating an awareness about the detrimental effects of constricted forms of masculinity on boys and men and their relationships with others; and b) developing remedial approaches to psychotherapy that are designed to help boys and men recover from dysfunctional masculinity. The purpose of this article is to expand this literature by introducing the positive psychology/positive masculinity (PPPM) framework, which emphasizes male strengths as the starting point for psychotherapy with boys and men. The central principles of the PPPM framework are described, and the application of the PPPM model with an adult man in psychotherapy is presented. The implications of the PPPM model for future practice and research pertaining to boys, men, and masculinity are discussed.


Breast cancer risk factors and second primary malignancies among women with breast cancer.
To examine the association between breast cancer risk factors and second primary cancers (independent diagnoses occurring at least 12 months after the initial breast cancer diagnosis) among breast cancer survivors. In this population-based study, cancer outcomes among breast cancer survivors first diagnosed during 1987-2000 were investigated. Invasive breast cancer cases were identified from the statewide tumor registry and interviewed regarding their pre-diagnosis risk factors, including reproductive and lifestyle characteristics, approximately 1 year after diagnosis. Data on second primary cancers (not recurrences) and deaths were obtained by linkage with tumor registry reports and death certificates through December 31, 2002. Hazard ratios (HR) were estimated using proportional hazards regression stratified by age and adjusted for stage and other factors. Among the 10,953 breast cancer cases, 10.8% experienced a second cancer diagnosis within an average of 7 years (including 488 breast, 132 colorectal, 113 endometrial, and 36 ovarian cancers). Risk of a second primary breast cancer increased according to low parity (P = 0.002), older age at menopause (P = 0.08), greater body mass index (P = 0.003) and adult weight gain (P = 0.02), and a family history of breast cancer-particularly among women with 2 or more first-degree affected relatives (HR = 1.8, 95% CI: 1.1-2.9). Reduced risk of colorectal cancer after breast cancer was observed in relation to older ages at menarche (P = 0.05), younger age at menopause (P = 0.04), postmenopausal hormone use (HR = 0.4, 95% CI: 0.3-0.7), normal body mass index (P = 0.07), and infrequent alcohol consumption (P = 0.01). Second endometrial cancer risk was associated with increasing body mass index (P < 0.01) and adult weight gain (P = 0.03). Risk of second ovarian cancer appeared related to recent alcohol intake and family history of breast cancer. Women who reported consuming any alcohol appeared to have a 55% reduction in ovarian cancer risk (95% CI: 0.2-1.0) compared to non-drinkers, while having 2 or more first-degree relatives with breast cancer was associated with an increased risk of ovarian cancer (HR = 4.3, 95% CI: 1.3-14.6). This study suggests that family history of breast cancer as well as potentially modifiable characteristics including body weight, alcohol intake, and postmenopausal hormone use may be associated with risk of a second cancer diagnosis among breast cancer cases.


Attempting to disentangle the relationship between impulsivity and longitudinal self-harm: Epidemiological analysis of UK household survey data.
Impulsivity may be an important risk factor in terms of future self-harm. However, the extent of this, whether it may relate to self-harm that is new in onset and/or repetition of self-harm, and the detail of any interaction with mood instability (MI) and childhood sexual abuse (CSA) requires detailed examination. We used the 2000 Adult Psychiatry Morbidity Survey and an 18-month follow-up data to test hypotheses relating to the role of impulsivity, CSA and MI in the inception and persistence of self-harm. We assessed associations of impulsivity with (1) suicidal self-harm (SSH) and (2) non-SSH (NSSH) at baseline and follow-up, controlling for confounders including MI. Finally, we tested whether impulsivity mediated the relationship between CSA and self-harm. A total of 8,580 respondents were assessed at baseline and 2,406 at follow-up as planned. Impulsivity significantly predicted emergence of new NSSH at 18-month follow-up even after adjustment for MI and other confounders. Impulsivity did not significantly predict repetition of NSSH, or repetition or new inception of SSH, even before inclusion of MI in the model. However, the absolute numbers involved were small. Cross-sectionally, impulsivity was a stronger mediator of the link between CSA and SSH (13.1%) than that between CSA and NSSH (4.8%). Impulsivity may increase the risk of future development of NSSH independently of MI, which is clinically important for risk assessment. The involvement of impulsivity in the repetition of self-harm generally appears less certain. However, impulsivity may have a role in SSH in the context of previous CSA.


Using data from monitoring combined sewer overflows to assess, improve, and maintain combined sewer systems.
Using low-cost sensors, data can be collected on the occurrence and duration of overflows in each combined sewer overflow (CSO) structure in a combined sewer system (CSS). The collection and analysis of real data can be used to assess, improve, and maintain CSSs in order to reduce the number and impact of overflows. The objective of this study was to develop a methodology to evaluate the performance of CSSs using low-cost monitoring. This methodology includes (1) assessing the capacity of a CSS using overflow duration and rain volume data, (2) characterizing the performance of CSO structures with statistics, (3) evaluating the compliance of a CSS with government guidelines, and (4) generating decision tree models to provide support to managers for making decisions about system maintenance. The methodology is demonstrated with a case study of a CSS in La Garriga, Spain. The rain volume breaking point from which CSO structures started to overflow ranged from 0.6 mm to 2.8 mm. The structures with the best and worst performance in terms of overflow (overflow probability, order, duration and CSO ranking) were characterized. Most of the obtained decision trees to predict overflows from rain data had accuracies ranging from 70% to 83%. The results obtained from the proposed methodology can greatly support managers and engineers dealing with real-world problems, improvements, and maintenance of CSSs.


Are severe depressive symptoms associated with infertility-related distress in individuals and their partners?
Are severe depressive symptoms in women and men associated with individual and dyadic infertility-related stress in couples undergoing infertility treatment? Severe depressive symptoms were significantly associated with increased infertility-related distress at both the individual and partner level. WHAT IS KNOWN ALREADY?: An infertility diagnosis, the stress of medical treatments and a prior history of depression are risk factors for future depression in those undergoing fertility treatments. Studies examining the impact of severe depressive symptoms on infertility-related distress in couples are lacking. This cross-sectional study included 1406 couples who were consecutively referred patients undergoing fertility treatments in Denmark in the year 2000. A total of 1049 men and 1131 women were included in the study. Participants were consecutively referred patients undergoing a cycle of medically assisted reproduction treatment at five Danish public and private clinics specializing in treating fertility patients. Severe depressive symptoms were measured by the Mental Health Inventory 5 from the Short Form Health Survey 36. Infertility distress was measured by the COMPI Fertility Problem Stress Scales. Multilevel modelling using the actor-partner interdependence model was used to study the couple as the unit of analysis. Severe depressive symptoms were reported in 11.6% of women and 4.3% of men, and were significantly associated with increased infertility-related distress at the individual and partner level. There was no significant interaction for gender indicating that men and women did not differ in how severe depressive symptoms were associated with infertility distress. Because of the cross-sectional study design, the study findings only show an association between severe depressive symptoms to individual and partner distress at a single point in time; however, nothing is known about causality. This study adds to the growing body of literature using the couple as the unit of analysis to study the relationship between depression and infertility distress. Recommendations for medical and mental health professionals that underscore the potential risk factors for depressed men and women who are pursuing infertility treatments are provided. Additional studies using a longitudinal study design to track the impact of depression on distress over the course of the infertility treatment cycle would be valuable for increasing our understanding of the complex relationship that exists between these psychosocial factors. Authors Brennan Peterson and Matthew Pirritano have no financial disclosures for this study. Camilla Sandal Sejbaek and Lone Schmidt have received research grants from the Danish Health Insurance Foundation (J. nr. 2008B105) and Merck Sharp & Dohme. The funders had no influence on the data collection, analyses or conclusions of the study.


Spatial patterns of medium and large size mammal assemblages in várzea and terra firme forests, Central Amazonia, Brazil.
Várzea forests account for 17% of the Amazon basin and endure an annual inundation that can reach 14 m deep during 6-8 months. This flood pulse in combination with topography directly influences the várzea vegetation cover. Assemblages of several taxa differ significantly between unflooded terra firme and flooded várzea forests, but little is known about the distribution of medium and large sized terrestrial mammals in várzea habitats. Therefore, our goal was to understand how those habitats influence mammalian species distribution during the dry season. Specifically, we: (1) compared the species composition between a terra firme (Amanã Sustainable Development Reserve) and a várzea forest (Mamirauá Sustainable Development Reserve); and (2) tested the influence of the várzea habitat classes on the number of records, occurrence and species composition of mammalian assemblages. The sampling design in each reserve consisted of 50 baited camera trap stations, with an overall sampling effort of 5015 camera trap days. We used Non-Metric Multidimension Scaling (NMDS) to compare species composition between terra firme and várzea forests, and used Generalized Linear Models (GLM) to assess how habitat types and a habitat diversity index affect mammal distributions. We recorded 21 medium and large sized mammalian species, including 20 species in terra firme and only six in várzea (3443 records). Flood pulse and isolation in várzea forest drove the dissimilarity between these two forest types. In várzea forest, medium size mammals, in general, avoided habitats associated with long flooding periods, while jaguars (Panthera onca) appeared to prefer aquatic/terrestrial transition zones. Habitats that remain dry for longer periods showed more mammalian occurrence, suggesting that dispersion via soil is important even for semi-arboreal species. This is the first study to evaluate differential use of várzea habitats by terrestrial mammalian assemblages.


Identification of aspirated radiolucent foreign bodies in the pediatric airway using digital tomosynthesis: a multireader phantom study.
Purpose: Foreign body aspiration is difficult to diagnose because many aspirated foreign bodies are low density or radiolucent. Digital radiographs (DR) are poor at detecting radiolucent foreign bodies. Digital tomosynthesis (DTS) has been shown to be ideally suited for applications where DR is insensitive and the increased dose from computed tomography (CT) is not justified. Our objective was to determine if DTS can be a practical alternative to DR and CT in the diagnosis of foreign body aspiration. Approach: A phantom approximating the densities of a pediatric chest was constructed. Radiolucent foreign bodies were placed in the airways. Seven pediatric radiologists assessed DTS and DR images with and without simulated breathing motion. Two rounds were performed with fixed exposure techniques and then automatic exposure control techniques. Interobserver agreement was evaluated using Fleiss' kappa. Results: DTS and DR images using fixed exposure techniques performed very poorly with accuracies of 42% to 60%. DTS with automatic exposure control techniques increased accuracy to 84% for a stationary phantom, but the accuracy dropped to 70% in a phantom with simulated motion. DTS outperformed DR, with DR accuracies of 60% and 63% for stationary simulations and motion, respectively. Interobserver agreement was poor with Fleiss' kappa of 0.476. Conclusion: DTS is superior to DR for radiolucent foreign body detection. However, the overall accuracy and interobserver agreement are likely too low for this modality to be clinically useful.


Mechanisms of quinolone resistance and clonal relationship among Aeromonas salmonicida strains isolated from reared fish with furunculosis.
The mechanisms of resistance to quinolone and epidemiological relationships among A. salmonicida strains isolated from diseased fish in French marine farms from 1998 to 2000 were investigated. The quinolone resistance-determining regions of the gyrA and parC genes of 12 clinical A. salmonicida isolates with different levels of quinolone susceptibility were sequenced. MICs were determined in the presence of the efflux pump inhibitor (EPI) Phe-Arg beta-naphthylamide and E(max) values (MIC without EPI/MIC in the presence of EPI) were calculated. Isolates fell into two classes: (i) those that had a wild-type gyrA gene with oxolinic acid MIC </= 0.5, flumequine MIC </= 1 and ciprofloxacin MIC </= 0.25 micro g ml(-1); and (ii) those that had a single mutation in gyrA encoding Asp-87 --> Asn with oxolinic acid MIC >/= 2, flumequine MIC >/= 4 and ciprofloxacin MIC >/= 0.125 micro g ml(-1). No mutations were found in parC. High E(max) values obtained for flumequine and oxolinic acid (up to 16 and 8, respectively, for the most resistant isolates of the two classes) indicated an important contribution of efflux to the resistance phenotype. Flumequine accumulation experiments confirmed that high E(max) values were associated with a much lower level of accumulation. PCR/RFLP assays conducted on 34 additional isolates showed the presence of a mutation at codon 87 of gyrA in nearly all the quinolone-resistant isolates. This finding, together with PFGE typing results, strongly suggests a common clonal origin of these quinolone-resistant isolates.


Influence of different durations of electroacupuncture stimulation on skin blood flow and muscle blood volume.
To determine whether skin blood flow (SBF) and muscle blood volume (MBV) responses differ according to the duration of electroacupuncture (EA) stimulation. Two experiments were conducted. In Experiment 1, healthy male students (n=20) were randomly divided into two groups (an EA group and a no-stimulation group). In Experiment 2, healthy male students (n=37) were randomly divided into three groups with different stimulation durations of EA (5, 10 and 15 min). EA stimulation on the quadriceps femoris muscle was administered with a frequency of 1 Hz. SBF and MBV were estimated before, during and after stimulation. In Experiment 1 there was a significant difference between the groups (p=0.001). In the EA stimulation group, MBV increased immediately following EA (p=0.045) and 5 min (p=0.005) and 10 min (p=0.002) after EA compared with baseline. No significant change was observed in the no-stimulation group. In Experiment 2 there was no significant difference between the groups. All three stimulation durations (5, 10 and 15 min) yielded increases in MBV after stimulation compared with baseline. SBF following stimulation for 5 and 10 min was increased compared with baseline. Based on these findings, we consider that 10 min EA stimulation could be a sufficient duration to induce a blood flow response in a clinical situation when increasing the blood flow is desirable.


An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen.
Existing murine models of asthma lack many of the inflammatory and epithelial changes that are typical of the human disease. Moreover, these models are frequently complicated by allergic alveolitis. High IgE responder BALB/c mice were systemically sensitised to ovalbumin and chronically challenged with low particle mass concentrations of aerosolised ovalbumin. Titres of antiovalbumin IgE in serum were measured at two weekly intervals by enzyme immunoassay, accumulation of inflammatory cells and histopathological abnormalities of the epithelium were quantified morphometrically in the trachea and the lungs, and airway reactivity was assessed by measuring bronchoconstriction following intravenous administration of methacholine. Mice sensitised by two intraperitoneal injections of ovalbumin developed high titres of IgE antibodies to ovalbumin. Following exposure to low concentrations of aerosolised antigen for up to eight weeks these animals developed a progressive inflammatory response in the airways, characterised by the presence of intraepithelial eosinophils and by infiltration of the lamina propria with lymphoid/mononuclear cells, without associated alveolitis. Goblet cell hyperplasia/metaplasia was induced in the intrapulmonary airways, while epithelial thickening and subepithelial fibrosis were evident following chronic exposure. In parallel, the mice developed increased sensitivity to induction of bronchospasm, as well as increased maximal reactivity. Non-immunised mice exposed to aerosolised ovalbumin had low or absent antiovalbumin IgE and did not exhibit inflammatory or epithelial changes, but developed airway hyperreactivity. This experimental model replicates many of the features of human asthma and should facilitate studies of pathogenetic mechanisms and of potential therapeutic agents.


Ultrafine particle deposition in subjects with asthma.
Ambient air particles in the ultrafine size range (diameter < 100 nm) may contribute to the health effects of particulate matter. However, there are few data on ultrafine particle deposition during spontaneous breathing, and none in people with asthma. Sixteen subjects with mild to moderate asthma were exposed for 2 hr, by mouthpiece, to ultrafine carbon particles with a count median diameter (CMD) of 23 nm and a geometric standard deviation of 1.6. Deposition was measured during spontaneous breathing at rest (minute ventilation, 13.3 +/- 2.0 L/min) and exercise (minute ventilation, 41.9 +/- 9.0 L/min). The mean +/- SD fractional deposition was 0.76 +/- 0.05 by particle number and 0.69 +/- 0.07 by particle mass concentration. The number deposition fraction increased as particle size decreased, reaching 0.84 +/- 0.03 for the smallest particles (midpoint CMD = 8.7 nm). No differences between sexes were observed. The deposition fraction increased during exercise to 0.86 +/- 0.04 and 0.79 +/- 0.05 by particle number and mass concentration, respectively, and reached 0.93 +/- 0.02 for the smallest particles. Experimental deposition data exceeded model predictions during exercise. The deposition at rest was greater in these subjects with asthma than in previously studied healthy subjects (0.76 +/- 0.05 vs. 0.65 +/- 0.10, p < 0.001). The efficient respiratory deposition of ultrafine particles increases further in subjects with asthma. Key words: air pollution, asthma, deposition, dosimetry, inhalation, ultrafine particles.


Radiofrequency ablation of renal tumors in the solitary kidney.
Radiofrequency ablation (RFA) is a minimally invasive therapy aimed at maximal preservation of renal function in the nonsurgical renal mass patient. We evaluate our experience with RFA of renal tumors in the solitary kidney. A retrospective review of all patients with a solitary kidney treated with RFA for renal mass was performed. Two radiologists reviewed all images. From December 2001 to June 2006, 55 renal tumors were treated with RFA in 30 patients with a solitary kidney. Percutaneous approach was used in 44 tumors (26 patients) and intraoperative open approach in 11 tumors (4 patients). Average mass size was 2.0 cm (1.2-5.4). Biopsy performed prior to ablation in 14 tumors showed renal cell carcinoma in 12 (86%) and was non diagnostic in 2 (14%). There were no major post procedural complications. Initial technical success was noted in 98% of tumors in 97% of patients. Average follow-up with contrast enhanced CT or MRI was 25 months (3-47) in 26 patients (50 tumors) and showed local tumor control in 100%. No difference in preoperative and postoperative calculated creatinine clearance was noted (p = 0.072). There was no difference in systolic (p = 0.102) and diastolic (p = 0.790) blood pressure pre and post ablation. RFA of renal masses in the solitary kidney appears to be a safe, minimally invasive alternative to open surgical resection in properly selected patients. Local tumor control was achieved with no adverse effects on renal function and blood pressure in this series.


Analytical performance of μ-groove silicon attenuated total reflection waveguides.
The analytical performance of micromachined μ-groove silicon attenuated total reflection (ATR) elements has been evaluated in a comparison of Fourier-transform infrared (FTIR) and quantum cascade laser (QCL) spectroscopy operating at mid-infrared (MIR) wavelengths. μ-Groove silicon ATR elements are highly efficient micromachined waveguides fabricated at a wafer scale at such low cost that they may be considered a consumable for single-time-use, e.g., in medical application scenarios. Herein, exemplary analytes haven been used for reliably evaluating their analytical performance (i.e., acetate and carbonate) in terms of sensitivity, noise level, and achievable limits of detection in a comparison of broadband vs. narrowband infrared spectroscopy.


Impact of diabetes and smoking on mortality in tuberculosis.
Diabetes mellitus is a risk factor for tuberculosis (TB) disease. There is evidence that diabetes also influences TB severity and treatment outcomes but information is incomplete and some published results have been inconsistent. A longitudinal cohort study was conducted at the National Masan Tuberculosis Hospital in the Republic of Korea. Subjects presenting with a first episode of TB or for retreatment of TB were followed from enrollment through completion of treatment. Demographic, clinical, and microbiological variables were recorded, along with assessment of outcomes. Results were compared in TB patients with and without diabetes or smoking history. Data were adjusted for gender, age, cohort, educational level and alcohol consumption. The combined cohorts comprised 657 subjects. Diabetes was present in 25% and was associated with greater radiographic severity and with recurrent or relapsed TB. Diabetes and cigarette smoking independently increased the risk of death in the first 12 months after enrollment. Estimating the combined impact of diabetes and smoking yielded a hazard ratio of 5.78. Only 20% of diabetic subjects were non-smokers; 54% smoked ≥1 pack daily. In this cohort, the impact of diabetes on mortality was greater in patients younger than 50 years, compared to older patients. In this cohort of Korean patients, diabetes exacerbated the severity of TB disease. Diabetic subjects who smoked ≥1 pack of cigarettes daily were at particularly high risk of death from TB. Strategies to improve TB outcomes could productively focus resources for patient education and TB prevention on the vulnerable population of younger diabetics, particularly those who also smoke.


Covert processing of facial expressions by people with Williams syndrome.
Although individuals with Williams Syndrome (WS) are empathic and sociable and perform relatively well on face recognition tasks, they perform poorly on tasks of facial expression recognition. The current study sought to investigate this seeming inconsistency. Participants were tested on a Garner-type matching paradigm in which identities and expressions were manipulated simultaneously as the relevant or irrelevant dimensions. Performance of people with WS on the expression-matching task was poor and relied primarily on facilitation afforded by congruent identities. Performance on the identity matching task came close to the level of performance of matched controls and was significantly facilitated by congruent expressions. We discuss potential accounts for the discrepant processing of expressions in the task-relevant (overt) and task-irrelevant (covert) conditions, expanding on the inherently semantic-conceptual nature of overt expression matching and its dependence on general cognitive level.


Effect of Virtual Reality Perspective-Taking on Related and Unrelated Contexts.
Virtual reality perspective-taking (VRPT) experiences effectively increase both empathy and prosocial behaviors toward related social targets (e.g., cutting down a tree in virtual reality increases concern for the environment). This project tests the prediction that empathy is analogous to a muscle that increases with practice and can transfer to unrelated contexts instead of being a mental state that increases only for a specific context or target. This study examines the extent to which VRPT experiences can train empathic skills that are applied to unrelated social targets and contexts. Two thirds of the participants engaged in VRPT experiences either showing what it is like to become homeless or how ocean acidification affects the marine environment. A third of the participants were in the control condition and did not complete a VRPT task. Results replicate previous findings showing that VRPT tasks increase related context empathy and prosocial behaviors; however, the results on VRPTs effect on empathy and prosocial behaviors for unrelated contexts were mixed. The VRPT ocean acidification task was more effective at inducing empathy for the homeless, an unrelated social target, than the control condition, but the empathy-transfer effect did not occur from the homeless context to the ocean context. Replicating previous work, participants who experienced what it is like to become homeless signed a petition supporting the homeless at significantly higher rates than participants in the control condition. These findings show that transfer of empathy from one context to another is possible, but this transfer does not occur for all contexts.


Schistosoma haematobium infection and asymptomatic bacteriuria in young South African females.
Schistosoma haematobium eggs can induce lesions in the urinary and genital tract epithelia, as eggs pass through or get trapped in the tissue. Local inflammatory reactions induced by S. haematobium eggs might affect the ability of bacteria to establish mucosal super-infection foci. S. haematobium infection and asymptomatic bacteriuria can both portray haematuria, proteinuria and leukocyturia. This shared set of proxy diagnostic markers could fuel routine misdiagnosis in S. haematobium endemic areas. Furthermore, S. haematobium infected individuals might be at a higher risk of contracting bacterial urinary tract infections, which could manifest either as symptomatic or asymptomatic bacteriuria. The aim of the current study was to explore whether schistosomal lesions are susceptible to super-infection by bacteria measured as asymptomatic bacteriuria. S. haematobium infection was determined by microscopy of urine samples. Furthermore, urine samples were tested with dipslides for asymptomatic bacteriuria and with dipsticks for haematuria, proteinuria and leukocytes. We found no association between asymptomatic bacteriuria and S. haematobium infection in a sample of 1040 female primary and high school students from a schistosomiasis endemic area in KwaZulu-Natal, South Africa. Furthermore, it was demonstrated that asymptomatic bacteriuria is not a bias for use of micro-haematuria as a proxy diagnostic measure for S. haematobium infection in this population.


Critical neural substrates for correcting unexpected trajectory errors and learning from them.
Our proficiency at any skill is critically dependent on the ability to monitor our performance, correct errors and adapt subsequent movements so that errors are avoided in the future. In this study, we aimed to dissociate the neural substrates critical for correcting unexpected trajectory errors and learning to adapt future movements based on those errors. Twenty stroke patients with focal damage to frontal or parietal regions in the left or right brain hemispheres and 20 healthy controls performed a task in which a novel mapping between actual hand motion and its visual feedback was introduced. Only patients with frontal damage in the right hemisphere failed to correct for this discrepancy during the ongoing movement. However, these patients were able to adapt to the distortion such that their movement direction on subsequent trials improved. In contrast, only patients with parietal damage in the left hemisphere showed a clear deficit in movement adaptation, but not in online correction. Left frontal or right parietal damage did not adversely impact upon either process. Our findings thus identify, for the first time, distinct and lateralized neural substrates critical for correcting unexpected errors during ongoing movements and error-based movement adaptation.


Evidenced-based clinical practice guideline for management of newborn pain.
To facilitate the uptake of evidence and to reduce the evidence practice gap for management of newborn pain through the development of a clinical practice guideline. An audit of practice and an appraisal of clinical practice guidelines were undertaken to establish current practices and guideline availability for the management of newborn pain in 23 hospitals in Australia. Guidelines were appraised using the Appraisal of Guidelines for Research and Evaluation instrument. A literature search was undertaken to acquire the evidence for best practice for management of newborn pain. Neonatal units in 17 hospitals had clinical practice guidelines. Each was peer reviewed and assessed according to the domains of the Appraisal of Guidelines for Research and Evaluation instrument. There was lack of consistency across the guidelines. As a result, a best practice guideline was developed based on current best evidence and the Royal Australian College of Physicians recommendations. To facilitate an ongoing compliance with the guideline, an audit tool was included together with algorithms for procedural pain and pain assessment. The clinical practice guideline can be used by clinicians in varying settings such as the neonatal intensive care and special care unit. The document can be used to support existing practices or challenge clinicians to close the evidence practice gap for the management of newborn pain.


Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil.
To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.


Assessment of automated image analysis of breast cancer tissue microarrays for epidemiologic studies.
A major challenge in studies of etiologic heterogeneity in breast cancer has been the limited throughput, accuracy, and reproducibility of measuring tissue markers. Computerized image analysis systems may help address these concerns, but published reports of their use are limited. We assessed agreement between automated and pathologist scores of a diverse set of immunohistochemical assays done on breast cancer tissue microarrays (TMA). TMAs of 440 breast cancers previously stained for estrogen receptor (ER)-alpha, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), ER-beta, and aromatase were independently scored by two pathologists and three automated systems (TMALab II, TMAx, and Ariol). Agreement between automated and pathologist scores of negative/positive was measured using the area under the receiver operating characteristics curve (AUC) and weighted kappa statistics for categorical scores. We also investigated the correlation between immunohistochemical scores and mRNA expression levels. Agreement between pathologist and automated negative/positive and categorical scores was excellent for ER-alpha and PR (AUC range = 0.98-0.99; kappa range = 0.86-0.91). Lower levels of agreement were seen for ER-beta categorical scores (AUC = 0.99-1.0; kappa = 0.80-0.86) and both negative/positive and categorical scores for aromatase (AUC = 0.85-0.96; kappa = 0.41-0.67) and HER2 (AUC = 0.94-0.97; kappa = 0.53-0.72). For ER-alpha and PR, there was a strong correlation between mRNA levels and automated (rho = 0.67-0.74) and pathologist immunohistochemical scores (rho = 0.67-0.77). HER2 mRNA levels were more strongly correlated with pathologist (rho = 0.63) than automated immunohistochemical scores (rho = 0.41-0.49). Automated analysis of immunohistochemical markers is a promising approach for scoring large numbers of breast cancer tissues in epidemiologic investigations. This would facilitate studies of etiologic heterogeneity, which ultimately may allow improved risk prediction and better prevention approaches.


Cessation of vital signs monitored during lethal hemorrhage: a Swine study.
Two challenges of trauma triage are to identify wounded who are in danger of imminent death and to enable medics to determine if resuscitation is possible when making ?dead or alive? decisions on the battlefield. Hemorrhagic shock is the leading cause of death in combat injuries. The purpose of this study was to establish the sequence of vital sign cessation during lethal hemorrhage in swine. Our hypothesis was that brain electrical activity (electroencephalography [EEG]) and respiration are earlier indicators of imminent death than traditional modalities measured during triage, such as heart electrical activity (electrocardiography [ECG]) and blood pressure. Lethal hemorrhage was induced in anesthetized Yorkshire pigs. Vital sign modalities measured were respiration, heart electrical activity (ECG), heart sound, blood pressure (systemic arterial pressure), and brain electrical activity (EEG). The sequence of vital sign cessation was (1) respiration, (2) brain electrical activity (EEG), (3) heart sound, (4) blood pressure, and (5) heart electrical activity (ECG). Cessation of respiration occurred at approximately the same time that brain electrical activity stopped (?flatlined?) for 2 seconds and then resumed briefly before cessation; cessation of heart electrical activity occurred almost 8 minutes later. A 2-second EEG flatline and final respiration are useful event markers to indicate an opportunity to prevent irreversible brain damage from lethal hemorrhage. Since the 2-second EEG flatline and final respiration occur about 8 minutes before cessation of heart electrical activity (ECG), EEG and final respiration are earlier indicators of imminent death. The use of deployable noninvasive brain monitors implementing these findings can be live-saving on the battlefield as well is in civilian environments.


Human sensory neurons derived from pluripotent stem cells for disease modelling and personalized medicine.
In this concise Mini-Review we will summarize ongoing developments of new techniques to study physiology and pathophysiology of the peripheral sensory nervous system in human stem cell derived models. We will focus on recent developments of reprogramming somatic cells into induced pluripotent stem cells, neural differentiation towards neuronal progenitors and human sensory neurons. We will sum up the high potential of this new technique for disease modelling of human neuropathies with a focus on genetic pain syndromes, such as gain- and loss-of-function mutations in voltage-gated sodium channels. The stem cell derived human sensory neurons are used for drug testing and we will summarize their usefulness for individualized treatment identification in patients with neuropathic pain. The review will give an outlook on potential application of this technique as companion diagnostics and for personalized medicine.


Proteomic analysis of the maize rachis: potential roles of constitutive and induced proteins in resistance to Aspergillus flavus infection and aflatoxin accumulation.
Infection of the maize (Zea mays L.) with aflatoxigenic fungus Aspergillus flavus and consequent contamination with carcinogenic aflatoxin is a persistent and serious agricultural problem causing disease and significant crop losses worldwide. The rachis (cob) is an important structure of maize ear that delivers essential nutrients to the developing kernels and A. flavus spreads through the rachis to infect kernels within the ear. Therefore, rachis plays an important role in fungal proliferation and subsequent kernel contamination. We used proteomic approaches and investigated the rachis tissue from aflatoxin accumulation resistant (Mp313E and Mp420) and susceptible (B73 and SC212m) maize inbred lines. First, we compared rachis proteins from resistant and susceptible inbred lines, which revealed that the young resistant rachis contains higher levels of abiotic stress-related proteins and proteins from phenylpropanoid metabolism, whereas susceptible young rachis contains pathogenesis-related proteins, which are generally inducible upon biotic stress. Second, we identified A. flavus-responsive proteins in rachis of both resistant and susceptible genotypes after 10- and 35-day infection. Differential expression of many stress/defense proteins during rachis juvenility, maturation and after A. flavus challenge demonstrates that resistant rachis relies on constitutive defenses, while susceptible rachis is more dependent on inducible defenses.


Lack of relationship between serum gp70 levels and the severity of systemic lupus erythematosus in MRL/l mice.
In the MRL/l mouse, gp70 apparently plays a role as an autoantigen in the development of SLE. However, while gp70 may be an important pathogenetic element, it is not essential to MRL SLE, since elimination of most of the serum gp70 and virtually all of the immune complex gp70 from MRL/l-low gp70 congenic lines had no observable effect on the course or nature of the disease. Thus, while gp70 in the MRL/l mouse appears to be a convenient autoantigenic target when present in significant levels, in its absence the host appears capable of directing its aberrant immunologic responsiveness elsewhere with undiminished pathogenicity.


Chiropractic Management of Pregnancy-Related Lumbopelvic Pain: A Case Study.
The purpose of this case report is to describe chiropractic management of a patient with pregnancy-related lumbopelvic pain. A pregnant 35-year-old woman experienced insidious moderate to severe pregnancy-related lumbopelvic pain and leg pain at 32 weeks' gestation. Pain limited her endurance capacity for walking and sitting. Clinical testing revealed a left sacroiliac joint functional disturbance and myofascial trigger points reproducing back and leg pain. A diagnosis of pregnancy-related low back pain and pregnancy-related pelvic girdle pain was made. The patient was treated with chiropractic spinal manipulation, soft tissue therapy, exercises, and ergonomic advice in 13 visits over 6 weeks. She consulted her obstetrician for her weekly obstetric visits. At the end of treatment, her low back pain reduced from 7 to 2 on a 0-10 numeric pain scale rating. Functional activities reported such as walking, sitting, and traveling comfortably in a car had improved. This patient with pregnancy-related lumbopelvic pain improved in pain and function after chiropractic treatment and usual obstetric management.


The future of human cerebral cartography: a novel approach.
Cerebral cartography can be understood in a limited, static, neuroanatomical sense. Temporal information from electrical recordings contributes information on regional interactions adding a functional dimension. Selective tagging and imaging of molecules adds biochemical contributions. Cartographic detail can also be correlated with normal or abnormal psychological or behavioural data. Modern cerebral cartography is assimilating all these elements. Cartographers continue to collect ever more precise data in the hope that general principles of organization will emerge. However, even detailed cartographic data cannot generate knowledge without a multi-scale framework making it possible to relate individual observations and discoveries. We propose that, in the next quarter century, advances in cartography will result in progressively more accurate drafts of a data-led, multi-scale model of human brain structure and function. These blueprints will result from analysis of large volumes of neuroscientific and clinical data, by a process of reconstruction, modelling and simulation. This strategy will capitalize on remarkable recent developments in informatics and computer science and on the existence of much existing, addressable data and prior, though fragmented, knowledge. The models will instantiate principles that govern how the brain is organized at different levels and how different spatio-temporal scales relate to each other in an organ-centred context.


Midazolam premedication for Ketamine-induced emergence phenomenon: A prospective observational study.
Ketamine administration is known to induce hemodynamic pressor response and psychomimetic effects which could be attenuated by appropriate premedication. The present study was designed to evaluate the effect of midazolam on hemodynamic stability and postoperative emergence phenomenon following ketamine anesthesia. This was a prospective observational study including 30 adult patients with American Society of Anesthesiologists physical grades I and II scheduled for elective short surgeries under ketamine anesthesia. Patients were premedicated with midazolam (0.02 mg/kg intravenously) before the ketamine induction (1 mg/kg intravenously). Demographic data and hemodynamic variables were observed during the perioperative period. Pain score by visual analog scale score and psychomimetic effects were recorded postoperatively. The mean ± standard deviation of heart rate, systolic blood pressure, diastolic blood pressure, and respiratory rate were decreased postoperatively (85.3 ± 11.4, 120.7 ± 8.2, 79.2 ± 5.5, 13.5 ± 1.8, respectively) compared to intraoperative period (88.53 ± 14.1, 123.83 ± 13.8, 83 ± 9.1, 14.13 ± 2.0, respectively). There was statistically significant decrease in systolic (P = 0.03) and diastolic (P = 0.002) blood pressure, but not with heart rate and respiratory rate. Eighty percent of patients had no pain at ½ hour and 1 hour, while this increased to 90% at 2 hours postoperatively. Mild emergence delirium was noted in 13.3% and 16.7% at ½ hour and 1 hour, respectively, which decreased to 13.3% at 2 hours. Dreams were noticed in 20%, 27% and 10% of patients at ½ hour, 1 and 2 hours after surgery, respectively. Midazolam premedication in ketamine anesthesia effectively attenuated the hemodynamic pressor response and postoperative emergence phenomenon. Hence, the combination of midazolam with ketamine can be safely used for short surgical painful procedures in adults.


Cortex morphology in first-episode psychosis patients with neurological soft signs.
Schizophrenia is a complex brain disorder associated with numerous etiological factors and pathophysiological pathways leading to multiple clinical outcomes. Compelling evidence suggests that deviations in neurodevelopmental processes are a major risk factor of schizophrenia. The identification of patients with high neurodevelopmental deviance is an important issue as it could help to identify homogeneous subgroups of patients with similar pathophysiological pathways, a key step to decipher the etiology of this complex condition. Several clinical arguments suggest that schizophrenia patients with Neurological Soft Signs (NSS)--ie, observable defects in motor coordination, motor integration, and sensory integration--would have high neurodevelopmental deviance. Based on the analysis of magnetic resonance imaging of 44 first-episode psychosis patients, we compared the cortex morphology, a marker of brain development, in patients with NSS vs patients with nonsignificant NSS. The cortex morphology was automatically assessed from three-dimensional global sulcal index (g-SI, the ratio between total sulcal area and outer cortex area) and regional sulcal indexes (r-SI, the ratio between the area of pooled labeled sulci and the total outer cortex area). Patients with NSS were found to have a lower g-SI in both hemispheres and a lower r-SI in left dorsolateral prefrontal and right lateral occipital cortices. Exploratory analyses revealed correlations between NSS dimensions and r-SI in distinct cortical areas, including dorsolateral and medial prefrontal cortices, lateral temporal, occipital, superior parietal, and medial parieto-occipital cortices. These findings provide evidence of distinct neurodevelopmental pathways in patients with NSS as compared with patients with nonsignificant NSS.


Dorsal anterior cingulate cortex and the value of control.
Debates over the function(s) of dorsal anterior cingulate cortex (dACC) have persisted for decades. So too have demonstrations of the region's association with cognitive control. Researchers have struggled to account for this association and, simultaneously, dACC's involvement in phenomena related to evaluation and motivation. We describe a recent integrative theory that achieves this goal. It proposes that dACC serves to specify the currently optimal allocation of control by determining the overall expected value of control (EVC), thereby licensing the associated cognitive effort. The EVC theory accounts for dACC's sensitivity to a wide array of experimental variables, and their relationship to subsequent control adjustments. Finally, we contrast our theory with a recent theory proposing a primary role for dACC in foraging-like decisions. We describe why the EVC theory offers a more comprehensive and coherent account of dACC function, including dACC's particular involvement in decisions regarding foraging or otherwise altering one's behavior.


Macrolide-resistant Mycoplasma pneumoniae: its role in respiratory infection.
Although the clinical relevance of antibiotic treatment in influencing the natural course of Mycoplasma pneumoniae-associated respiratory diseases is questioned by some physicians, most experts suggest that antibiotics should be systematically used in patients with M. pneumoniae respiratory infections, especially those involving the lower respiratory tract. Macrolides (MLs), tetracyclines (TCs) and fluoroquinolones (FQs) are the drugs of choice for M. pneumoniae infection, but only MLs are recommended for children. The main aim of this review is to analyse what is known about M. pneumoniae resistance to MLs and discuss the most reasonable approach to treating patients with M. pneumoniae infection at a time when resistant strains are being increasingly detected. The results show that no change in ML prescription is needed in countries in which the incidence of ML-resistant M. pneumoniae is low; however, in countries in which ML-resistant M. pneumoniae strains are very common, the replacement of an ML by a TC or FQ should be considered depending on the severity of the disease. A number of cases treated with ineffective antibiotics have shown similar outcomes to those observed in patients infected by susceptible strains. This seems to indicate that there is no need to change ML use systematically in the case of mild to moderate disease, but other antibiotics should be prescribed if the symptoms persist or there are signs of a clinical deterioration.


A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa.
Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.