Changes in Actinomycetes community structure under the influence of Bt transgenic brinjal crop in a tropical agroecosystem.
The global area under brinjal cultivation is expected to be 1.85 million hectare with total fruit production about 32 million metric tons (MTs). Brinjal cultivars are susceptible to a variety of stresses that significantly limit productivity. The most important biotic stress is caused by the Brinjal fruit and shoot Borer (FSB) forcing farmers to deploy high doses of insecticides; a matter of serious health concern. Therefore, to control the adverse effect of insecticides on the environment including the soil, transgenic technology has emerged as the effective alternative. However, the reports, regarding the nature of interaction of transgenic crops with the native microbial community are inconsistent. The effect of a Bt transgenic brinjal expressing the bio-insecticidal protein (Cry1Ac) on the rhizospheric community of actinomycetes has been assessed and compared with its non-transgenic counterpart. Significant variation in the organic carbon observed between the crops (non-Bt and Bt brinjal) may be due to changes in root exudates quality and composition mediated by genetic attributes of Bt transgenic brinjal. Real time quantitative PCR indicated significant differences in the actinomycetes- specific 16S rRNA gene copy numbers between the non-Bt (5.62-27.86) × 1011 g-1 dws and Bt brinjal planted soil (5.62-24.04) × 1011 g-1 dws. Phylogenetic analysis indicated 14 and 11, actinomycetes related groups in soil with non-Bt and Bt brinjal crop, respectively. Micrococaceaea and Nocardiodaceae were the dominant groups in pre-vegetation, branching, flowering, maturation and post-harvest stage. However, Promicromonosporaceae, Streptosporangiaceae, Mycobacteriaceae, Geodermatophilaceae, Frankiaceae, Kineosporaceae, Actisymmetaceae and Streptomycetaceae were exclusively detected in a few stages in non-Bt brinjal rhizosphere soil while Nakamurellaceae, Corynebactericeae, Thermomonosporaceae and Pseudonocardiaceae in Bt brinjal counterpart. Field trails envisage that cultivation of Bt transgenic brinjal had negative effect on organic carbon which might be attributed to genetic modifications in the plant. Changes in the organic carbon also affect the actinomycetes population size and diversity associated with rhizospheric soils of both the crops. Further long-term study is required by taking account the natural cultivar apart from the Bt brinjal and its near-isogenic non-Bt brinjal with particular reference to the effects induced by the Bt transgenic brinjal across different plant growth stages.


Cervical intraepithelial neoplasia is not associated with elevated serum neopterin levels.
Neopterin, a marker of cellular immune activation, was elevated in patients who had cervical cancer in previous studies. To examine neopterin in the presence of precursors to cervical cancer (i.e., cervical intraepithelial neoplasia) we measured serum levels in 185 colposcopy patients in Jamaica, a country with high cervical cancer incidence, and in 72 age-matched Jamaican women selected from a large population-based sample. We also measured serum levels of beta-2-microglobulin, another commonly used marker of immune activation. Neopterin and beta-2-microglobulin levels were not elevated in colposcopy patients; neither were they related to severity of cervical neoplasia. In multivariable analysis, neither adjustments for detection of cervical human papillomavirus DNA by PCR nor detection of antibodies to human T-cell lymphotropic virus type I (a retrovirus endemic to Jamaica) altered our findings. The absence of a serologically detectable increase in cellular immune activation linked to cervical intraepithelial neoplasia suggests that the immunological response to cervical intraepithelial neoplasia does not involve substantial systemic cellular immune activation.


Contraceptive discontinuation and non-use in Santarém, Brazilian Amazon.
In this paper we discuss the causes of non-adherence to reversible contraceptives, especially hormonal methods, among women in rural Santarém in the Brazilian Amazon. The analysis is based on questionnaires with 398 women and visits to health centers. We consider the motives reported by women who: never used contraception; used some method in the past; and who at the time of the survey were using a different method from the ones they used in the past. The results indicate a rejection of hormonal contraception and a preference for female sterilization, an option possibly influenced by the characteristics of health services in the region. The side effects of hormonal contraceptive use reported by part of the interviewees contribute to a generalized fear of the side effects even among women who have never used such methods. To improve women's health services in the Amazon, we recommend further studies of the relationship between reported side effects and available services and prescriptions, as well as an analysis of women's discourse and perceptions.


Cutoff scores in neurocognitive testing and symptom clusters that predict protracted recovery from concussions in high school athletes.
Many studies address diagnosing concussions, but few look at predicting prognosis. A previous discriminant function analysis showed that symptom clusters derived from the Post-Concussion Symptom Scale and Immediate Postconcussion Assessment and Cognitive Testing composite scores used together improved predictions of protracted recovery after a sports-related concussion. To determine cutoff scores in neurocognitive and Post-Concussion Symptom Scale symptom cluster scores when classifying protracted recovery in concussed athletes. 108 male high school football athletes completed a computer-based neurocognitive test battery (Immediate Postconcussion Assessment and Cognitive Testing) within a median of 2 days after injury. Patients completed graded exertional protocols requiring athletes to be symptom free at rest and during increasing levels of activity and had recovery of neurocognitive scores before return to play. After return to play, athletes were classified as protracted recovery (>14 days, n = 58) or short-recovery (≤14 days, n = 50). Receiver-operating characteristic curves analyzed each of the neurocognitive (verbal, visual, processing speed, and reaction time) and symptom cluster (migraine, cognitive, sleep, and neuropsychiatric) scores. Cutoffs for migraine cluster, cognitive cluster, visual memory, and processing speed were statistically significant. Cutoffs at 75%, 80%, and 85% sensitivity to predict protracted recovery for the migraine symptom cluster were 15 or greater, 18, 20; cognitive symptom cluster 18 or greater, 19, 22; visual memory 48 or less, 46, 44.5; and processing speed 24.5 or less, 23.46, 22.5, respectively. Eighty-percent sensitivity indicates that the corresponding cutoff correctly identify 80% of concussed athletes requiring protracted recovery. Specific cutoffs may help to set numerical thresholds for clinicians to predict which concussed athletes will have a protracted recovery.


Chondroitinase ABC combined with neural stem/progenitor cell transplantation enhances graft cell migration and outgrowth of growth-associated protein-43-positive fibers after rat spinal cord injury.
We previously reported that the transplantation of neural stem/progenitor cells (NSPCs) can contribute to the repair of injured spinal cord in adult rats and monkeys. In some cases, however, most of the transplanted cells adhered to the cavity wall and failed to migrate and integrate into the host spinal cord. In this study we focused on chondroitin sulfate proteoglycan (CSPG), a known constituent of glial scars that is strongly expressed after spinal cord injury (SCI), as a putative inhibitor of NSPC migration in vivo. We hypothesized that the digestion of CSPG by chondroitinase ABC (C-ABC) might promote the migration of transplanted cells and neurite outgrowth after SCI. An in vitro study revealed that the migration of NSPC-derived cells was inhibited by CSPG and that this inhibitory effect was attenuated by C-ABC pre-treatment. Consistently, an in vivo study of C-ABC treatment combined with NSPC transplantation into injured spinal cord revealed that C-ABC pre-treatment promoted the migration of the transplanted cells, whereas CSPG-immunopositive scar tissue around the lesion cavity prevented their migration into the host spinal cord in the absence of C-ABC pre-treatment. Furthermore, this combined treatment significantly induced the outgrowth of a greater number of growth-associated protein-43-positive fibers at the lesion epicentre, compared with NSPC transplantation alone. These findings suggested that the application of C-ABC enhanced the benefits of NSPC transplantation for SCI by reducing the inhibitory effects of the glial scar, indicating that this combined treatment may be a promising strategy for the regeneration of injured spinal cord.


Generating complex three-dimensional stimuli (Greebles) for haptic expertise training.
An apparatus is described that accurately measures response times and video records hand movements during haptic object recognition using complex three-dimensional (3-D) forms. The apparatus was used for training participants to become expert at perceptual judgments of 3-D objects (Greebles) using only their sense of touch. Inspiration came from previous visual experiments, and therefore training and testing protocols that were similar to the earlier visual procedures were used. Two sets of Greebles were created. One set (clay Greebles) was hand crafted from clay, and the other (plastic Greebles) was machine created using rapid prototyping technology. Differences between these object creation techniques and their impact on perceptual expertise training are discussed. The full set of these stimuli may be downloaded from www.psychonomic.org/archive/.


Greenhouse gas footprinting for small businesses--the use of input-output data.
To mitigate anthropogenic climate change greenhouse gas emissions (GHG) must be reduced; their major source is man's use of energy. A key way to manage emissions is for the energy consumer to understand their impact and the consequences of changing their activities. This paper addresses the challenge of delivering relevant, practical and reliable greenhouse gas 'footprint' information for small and medium sized businesses. The tool we describe is capable of ascribing parts of the total footprint to specific actions to which the business can relate and is sensitive enough to reflect the consequences of change. It provides a comprehensive description of all emissions for each business and sets them in the context of local, national and global statistics. It includes the GHG costs of all goods and services irrespective of their origin and without double accounting. We describe the development and use of the tool, which draws upon both national input-output data and process-based life cycle analysis techniques; a hybrid model. The use of national data sets the output in context and makes the results consistent with national and global targets, while the life cycle techniques provide a means of reflecting the dynamics of actions. The model is described in some detail along with a rationale and a short discussion of validity. As the tool is designed for small commercial users, we have taken care to combine rigour with practicality; parameterising from readily available client data whilst being clear about uncertainties. As an additional incentive, we also report on the potential costs or savings of switching activities. For users to benefit from the tool, they need to understand the output and know how much confidence they should place in the results. We not only describe an application of non-parametric statistics to generate confidence intervals, but also offer users the option of and guidance on adjusting figures to examine the sensitivity of the model to its components. It is important that the user does not see the model as a calculator that will generate one truth, but as a method of gaining insight and informing management decisions. We describe its application in tourism businesses in North West England as a demonstrator for the service sector remote from simple primary production, with brief case studies. We discuss its success compared to traditional approaches and outline further development work.


Real-world effectiveness of antipsychotic treatment in psychosis prevention in a 3-year cohort of 517 individuals at clinical high risk from the SHARP (ShangHai At Risk for Psychosis).
Antipsychotics are widely used for treating psychosis, but it is unclear whether they can also prevent psychosis. This study attempted a longitudinal evaluation of antipsychotics under real-world conditions in China to evaluate their effect on the rate of conversion to psychosis in individuals with a clinical high risk (CHR) of psychosis. A total of 517 CHR individuals were recruited between 2011 and 2016 and followed up for 3 years. Among these, 450 (87.0%) individuals completed follow-up, 108 (24.0%) showed conversion to psychosis and 309 (68.7%) received antipsychotics. The main outcome was conversion to psychosis. The sample was further stratified according to the severity of positive symptoms. Patients who did not receive antipsychotics showed a lower conversion rate than those who did (17.7% vs 26.9%; odds ratio [OR] = 0.660, 95% confidence interval [CI] = [0.442, 0.985], p = 0.035). In mild CHR cases, antipsychotic treatment was more likely to be associated with conversion to psychosis, compared with the no-antipsychotics group, with no such difference observed in severe CHR cases. Among those who received antipsychotics, monotherapy or low-dose treatment was associated with lower conversion rates. Our results did not favor any specific type of antipsychotics and suggested that a very small subgroup of CHR individuals with severe positive and general symptoms but mild negative symptoms may benefit from antipsychotic treatment. Administration of antipsychotics to CHR patients is potentially harmful with no preventive benefits. We do not recommend antipsychotic treatment for CHR individuals, which is practiced widely in China, and strongly advise caution if these drugs are used.


The sperm nucleus: chromatin, RNA, and the nuclear matrix.
Within the sperm nucleus, the paternal genome remains functionally inert and protected following protamination. This is marked by a structural morphogenesis that is heralded by a striking reduction in nuclear volume. Despite these changes, both human and mouse spermatozoa maintain low levels of nucleosomes that appear non-randomly distributed throughout the genome. These regions may be necessary for organizing higher order genomic structure through interactions with the nuclear matrix. The promoters of this transcriptionally quiescent genome are differentially marked by modified histones that may poise downstream epigenetic effects. This notion is supported by increasing evidence that the embryo inherits these differing levels of chromatin organization. In concert with the suite of RNAs retained in the mature sperm, they may synergistically interact to direct early embryonic gene expression. Irrespective, these features reflect the transcriptional history of spermatogenic differentiation. As such, they may soon be utilized as clinical markers of male fertility. In this review, we explore and discuss how this may be orchestrated.


The NF-kappaB inhibitor curcumin blocks sepsis-induced muscle proteolysis.
We tested the hypothesis that treatment of rats with curcumin prevents sepsis-induced muscle protein degradation. In addition, we determined the influence of curcumin on different proteolytic pathways that are activated in septic muscle (i.e., ubiquitin-proteasome-, calpain-, and cathepsin L-dependent proteolysis) and examined the role of NF-kappaB and p38/MAP kinase inactivation in curcumin-induced inhibition of muscle protein breakdown. Rats were made septic by cecal ligation and puncture or were sham-operated. Groups of rats were treated with three intraperitoneal doses (600 mg/kg) of curcumin or corresponding volumes of solvent. Protein breakdown rates were measured as release of tyrosine from incubated extensor digitorum longus muscles. Treatment with curcumin prevented sepsis-induced increase in muscle protein breakdown. Surprisingly, the upregulated expression of the ubiquitin ligases atrogin-1 and MuRF1 was not influenced by curcumin. When muscles from septic rats were treated with curcumin in vitro, proteasome-, calpain-, and cathepsin L-dependent protein breakdown rates were reduced, and nuclear NF-kappaB/p65 expression and activity as well as levels of phosphorylated (activated) p38 were decreased. Results suggest that sepsis-induced muscle proteolysis can be blocked by curcumin and that this effect may, at least in part, be caused by inhibited NF-kappaB and p38 activities. The results also suggest that there is not an absolute correlation between changes in muscle protein breakdown rates and changes in atrogin-1 and MuRF1 expression during treatment of muscle wasting.


Candidacidal activity of Crohn's disease neutrophils.
The ability of normal and Crohn's disease neutrophils to kill Candida albicans has been studied using neutrophils isolated from peripheral blood and suspended in phosphate buffered saline at 5 x 10(6) cells per ml. C albicans was grown to a stationary phase in broth culture and suspended in phosphate buffered saline at 10(7) organisms/ml. Neutrophils and Candida were then incubated together at 37 degrees C in a shaking water bath in the presence of fresh serum. At 30 and 60 minutes samples were withdrawn, neutrophils lysed, and Candida survival assessed by colony counting. Results were compared with control suspensions of Candida incubated with serum alone. After 30 and 60 minutes in the presence of autologous serum normal neutrophils had killed significantly more Candida than Crohn's disease neutrophils (mean (SD) 61.0 (16.7)% v 40.5 (16.2)% at 30 minutes, p less than 0.0001; 83.2 (7)% v 70.8) 16)% at 60 minutes, p less than 0.005). The results did not alter significantly when normal neutrophils were incubated with Candida in the presence of Crohn's disease serum instead of normal serum. When Crohn's disease neutrophils were incubated with Candida in the presence of normal serum instead of autologous serum there was some improvement in candidacidal ability at 30 minutes (48.9 (20.6)% v 40.5 (16.2)%, p less than 0.03) but not at 60 minutes. Phagocytosis, measured using a radiometric assay, was normal. Neutrophils from patients with Crohn's disease have an impaired ability to kill this granuloma provoking organism. It is not due to serum inhibitors or defective phagocytosis.


Water and its influence on the lithosphere-asthenosphere boundary.
The Earth has distinctive convective behaviour, described by the plate tectonics model, in which lateral motion of the oceanic lithosphere of basaltic crust and peridotitic uppermost mantle is decoupled from the underlying mechanically weaker upper mantle (asthenosphere). The reason for differentiation at the lithosphere-asthenosphere boundary is currently being debated with relevant observations from geophysics (including seismology) and geochemistry (including experimental petrology). Water is thought to have an important effect on mantle rheology, either by weakening the crystal structure of olivine and pyroxenes by dilute solid solution, or by causing low-temperature partial melting. Here we present a novel experimental approach to clarify the role of water in the uppermost mantle at pressures up to 6 GPa, equivalent to a depth of 190 km. We found that for lherzolite in which a water-rich vapour is present, the temperature at which a silicate melt first appears (the vapour-saturated solidus) increases from a minimum of 970 °C at 1.5 GPa to 1,350 °C at 6 GPa. We have measured the water content in lherzolite to be approximately 180 parts per million, retained in nominally anhydrous minerals at 2.5 and 4 GPa at temperatures above and below the vapour-saturated solidus. The hydrous mineral pargasite is the main water-storage site in the uppermost mantle, and the instability of pargasite at pressures greater than 3 GPa (equivalent to more than about 90 km depth) causes a sharp drop in both the water-storage capacity and the solidus temperature of fertile upper-mantle lherzolite. The presence of interstitial melt in mantle with more than 180 parts per million of water at pressures greater than 3 GPa alters mantle rheology and defines the lithosphere-asthenosphere boundary. Modern asthenospheric mantle acting as the source for mid-oceanic ridge basalts has a water content of 50-200 parts per million (refs 3-5). We show that this matches the water content of residual nominally anhydrous minerals after incipient melting of lherzolite at the vapour-saturated solidus at high pressure.


A layered electrospun and woven surgical scaffold to enhance endogenous tendon repair.
Surgical reattachments of tendon to bone in the rotator cuff are reported to fail in around 40% of cases. There are no adequate solutions to improve tendon healing currently available. Electrospun, sub-micron materials, have been extensively studied as scaffolds for tendon repair with promising results, but are too weak to be surgically implanted or to mechanically support the healing tendon. To address this, we developed a bonding technique that enables the processing of electrospun sheets into multi-layered, robust, implantable fabrics. Here, we show a first prototype scaffold created with this method, where an electrospun sheet was reinforced with a woven layer. The resulting scaffold presents a maximum suture pull out strength of 167N, closely matched with human rotator cuff tendons, and the desired nanofibre-mediated bioactivity in vitro and in vivo. This type of scaffold has potential for broader application for augmenting other soft tissues.


Non-communicable diseases in emergencies: a call to action.
Recent years have demonstrated the devastating health consequences of complex emergencies and natural disasters and thereby highlighted the importance of comprehensive and collaborative approaches to humanitarian responses and risk reduction. Simultaneously, noncommunicable diseases are now recognised as a real and growing threat to population health and development; a threat that is magnified by and during emergencies. Noncommunicable diseases, however, continue to receive little attention from humanitarian organisations in the acute phase of disaster and emergency response. This paper calls on all sectors to recognise and address the specific health challenges posed by noncommunicable diseases in emergencies and disaster situations. This publication aims to highlight the need for: • Increased research on morbidity and mortality patterns due to noncommunicable diseases during and following emergencies; • Raised awareness through greater advocacy for the issue and challenges of noncommunicable diseases during and following emergencies; • Incorporation of noncommunicable diseases into existing emergency-related policies, standards, and resources; • Development of technical guidelines on the clinical management of noncommunicable diseases in emergencies; • Greater integration and coordination in health service provision during and following emergencies; • Integrating noncommunicable diseases into practical and academic training of emergency workers and emergency-response coordinators.


Cholesterol granuloma of the frontal sinus.
It is common to see cholesterol granuloma in the mastoid air cells, less common in the orbit, and uncommon in the paranasal sinuses. Cholesterol granuloma is thought to be due to an interruption to normal aeration with impaired lymphatic drainage, resulting in a closed cavity where it may form. These expanding cysts cause bone destruction and compression of the surrounding structures that lead to clinical symptoms. Diagnosis and management of cholesterol granuloma cysts can be challenging. Magnetic resonance imaging (MRI) and computed tomographic (CT) scans are usually diagnostic. We present a rare case of cholesterol granuloma in the frontal sinus, few cases have been reported in the literature.


Miniature release events of glutamate from hippocampal neurons are influenced by the dystonia-associated protein torsinA.
TorsinA is an evolutionarily conserved AAA+ ATPase, and human patients with an in-frame deletion of a single glutamate (ΔE) codon from the encoding gene suffer from autosomal-dominant, early-onset generalized DYT1 dystonia. Although only 30-40% of carriers of the mutation show overt motor symptoms, most experience enhanced excitability of the central nervous system. The cellular mechanism responsible for this change in excitability is not well understood. Here we show the effects of the ΔE-torsinA mutation on miniature neurotransmitter release from neurons. Neurotransmitter release was characterized in cultured hippocampal neurons obtained from wild-type, heterozygous, and homozygous ΔE-torsinA knock-in mice using two approaches. In the first approach, patch-clamp electrophysiology was used to record glutamate-mediated miniature excitatory postsynaptic currents (mEPSCs) in the presence of the Na⁺ channel blocker tetrodotoxin (TTX) and absence of GABA(A) receptor antagonists. The intervals between mEPSC events were significantly shorter in neurons obtained from the mutant mice than in those obtained from wild-type mice. In the second approach, the miniature exocytosis of synaptic vesicles was detected by imaging the unstimulated release of FM dye from the nerve terminals in the presence of TTX. Cumulative FM dye release was higher in neurons obtained from the mutant mice than in those obtained from wild-type mice. The number of glutamatergic nerve terminals was also assessed, and we found that this number was unchanged in heterozygous relative to wild-type neurons, but slightly increased in homozygous neurons. Notably, in both heterozygous and homozygous neurons, the unitary synaptic charge during each mEPSC event was unchanged. Overall, our results suggest more frequent miniature glutamate release in neurons with ΔE-torsinA mutations. This change may be one of the underlying mechanisms by which the excitability of the central nervous system is enhanced in the context of DYT1 dystonia. Moreover, qualitative differences between heterozygous and homozygous neurons with respect to certain synaptic properties indicate that the abnormalities observed in homozygotes may reflect more than a simple gene dosage effect.


Compassion in nursing: exploring the perceptions of students and academics.
Compassion is integral to effective nursing practice, yet there is limited empirical research exploring this concept, particularly from a professional perspective. Aim To advance understanding of compassion from a professional perspective, specifically through the perceptions of students and academics from the fields of adult, child, learning disability and mental health nursing. A constructivist grounded theory study was undertaken, and a theoretical sampling strategy was used to guide the selection of appropriate participants. A total of 12 nursing students and eight nurse academics were interviewed to explore their perceptions of compassion in nursing between January and August 2018. The interview transcripts were analysed using grounded theory techniques. Four categories were identified from the interview data: character for compassion, competence for compassion, culture for compassion, and connections for compassion. These categories were interlinked, with each having the potential to influence the implementation of humanising approaches to care, which participants perceived to be fundamental to compassion. Compassion is a complex concept that can be influenced by biological, psychological and socio-contextual factors. Further consideration of these factors is required to support nurses to facilitate compassion through humanising approaches to care. The findings of this study advance the existing evidence to inform future policy, practice, education and research.


A review of non-pharmacological and pharmacological management of seasonal and perennial allergic conjunctivitis.
Allergic eye disease encompasses a group of hypersensitivity disorders which primarily affect the conjunctiva and its prevalence is increasing. It is estimated to affect 8% of patients attending optometric practice but is poorly managed and rarely involves ophthalmic assessment. Seasonal allergic conjunctivitis (SAC) is the most common form of allergic eye disease (90%), followed by perennial allergic conjunctivitis (PAC; 5%). Both are type 1 IgE mediated hypersensitivity reactions where mast cells play an important role in pathophysiology. The signs and symptoms are similar but SAC occurs periodically whereas PAC occurs year round. Despite being a relatively mild condition, the effects on the quality of life can be profound and therefore they demand attention. Primary management of SAC and PAC involves avoidance strategies depending on the responsible allergen(s) to prevent the hypersensitivity reaction. Cooled tear supplements and cold compresses may help bring relief. Pharmacological agents may become necessary as it is not possible to completely avoid the allergen(s). There are a wide range of anti-allergic medications available, such as mast cell stabilisers, antihistamines and dual-action agents. Severe cases refractory to conventional treatment require anti-inflammatories, immunomodulators or immunotherapy. Additional qualifications are required to gain access to these medications, but entry-level optometrists must offer advice and supportive therapy. Based on current evidence, the efficacy of anti-allergic medications appears equivocal so prescribing should relate to patient preference, dosing and cost. More studies with standardised methodologies are necessary elicit the most effective anti-allergic medications but those with dual-actions are likely to be first line agents.


Temperature effect on the immune defense functions of Arctic charr Salvelinus alpinus.
The Arctic charr Salvelinus alpinus is an endangered fish species in Finland, and thus farming is carried out mainly for stocking purposes. Farmed charr are susceptible to infection with atypical Aeromonas salmonicida (aAS). Losses of valuable brood stock will severely reduce the genetic diversity of stocked charr. No commercial vaccines are available to prevent aAS infection, and vaccines against furunculosis (caused by typical A. salmonicida, tAS) do not protect the charr against aAS infection. The effects of a metabolizable oil-adjuvanted, bivalent vaccine (containing killed aAS and A. salmonicida salmonicida bacteria) on the immune system of 1 yr old hatchery-reared charr originating from Lake Inari in Northern Finland were examined. Fish vaccination in Finland generally takes place either from October to November or from February to April, when the water temperature is low (1 to 3degrees C). The water temperature starts to increase in mid-May. Therefore, we also investigated whether post-vaccination (p.v.) temperature had an influence on the immune system of this cold-water fish species. The fish were immunized intraperitoneally at 2.9 degrees C at the end of April. After 52 d, during which the water temperature increased from 2.9 to 10.0 degrees C, the charr were exposed to 1 of 3 test temperatures: 10.3, 14.1 or 18.1 degrees C. Prior to vaccination, and 49, 75 and 103 d p.v., several immune parameters were measured in both unvaccinated and vaccinated charr. Vaccination induced a significant anti-aAS-specific antibody response, and increased plasma lysozyme activity at all p.v. temperatures. The haemolytic activity of the complement system was unaffected either by vaccination or p.v. temperatures. There was a slight positive correlation between p.v. temperature and lysozyme activity of the charr. The significant increase in lysozyme activity took place in vaccinated charr in the first 49 d p.v. as water temperatures increased from 2.9 to 10 degrees C. Furthermore, the highest activity of lysozyme in the plasma was observed 49 d p.v. Our results indicate that a rise in water temperature above 10 degrees C does not significantly enhance the vaccination response of charr. This could be one reason why farmed Arctic charr, which are well adapted to a cold climate, are highly susceptible to aAS infection in the summer.


A deep-coverage tomato BAC library and prospects toward development of an STC framework for genome sequencing.
Recently a new strategy using BAC end sequences as sequence-tagged connectors (STCs) was proposed for whole-genome sequencing projects. In this study, we present the construction and detailed characterization of a 15.0 haploid genome equivalent BAC library for the cultivated tomato, Lycopersicon esculentum cv. Heinz 1706. The library contains 129,024 clones with an average insert size of 117.5 kb and a chloroplast content of 1.11%. BAC end sequences from 1490 ends were generated and analyzed as a preliminary evaluation for using this library to develop an STC framework to sequence the tomato genome. A total of 1205 BAC end sequences (80.9%) were obtained, with an average length of 360 high-quality bases, and were searched against the GenBank database. Using a cutoff expectation value of <10(-6), and combining the results from BLASTN, BLASTX, and TBLASTX searches, 24.3% of the BAC end sequences were similar to known sequences, of which almost half (48.7%) share sequence similarities to retrotransposons and 7% to known genes. Some of the transposable element sequences were the first reported in tomato, such as sequences similar to maize transposon Activator (Ac) ORF and tobacco pararetrovirus-like sequences. Interestingly, there were no BAC end sequences similar to the highly repeated TGRI and TGRII elements. However, the majority (70.3%) of STCs did not share significant sequence similarities to any sequences in GenBank at either the DNA or predicted protein levels, indicating that a large portion of the tomato genome is still unknown. Our data demonstrate that this BAC library is suitable for developing an STC database to sequence the tomato genome. The advantages of developing an STC framework for whole-genome sequencing of tomato are discussed.


Effect of biologics in the level of cytokines in the synovial fluid of patients with ankylosing spondylitis.
Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), interleukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs. Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were analyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups. The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correlation among each other in the non-biologics group. However, there was no significant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group. Treatment with biologics affects the cytokine profile in inflammatory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.


Patterns and associated risk of perioperative use of anti-tumor necrosis factor in patients with rheumatoid arthritis undergoing total knee replacement.
The patterns and risks of perioperative use of anti-tumor necrosis factor (anti-TNF) medication in patients with rheumatoid arthritis (RA) are not well studied. We examined the patterns of perioperative anti-TNF use and risk of postoperative adverse events (AE) in patients undergoing total knee replacement (TKR). Retrospective cohort study with followup. RA cases within a TKR registry were identified by ICD-9 code (714.0) or self-report. Mailed questionnaires queried anti-TNF use and duration of RA. AE were determined by chart review and patient self-report, and included surgical site infection, pulmonary embolus, deep venous thrombosis, pneumonia, and any infection or re-operation within 6 months. There were 268 TKR cases with RA. The stop time for anti-TNF preoperatively correlated with dosing schedule; restart time was after wound healing. There were 7 surgical site infections (3%), one (0.4%) of which was a deep joint infection in bilateral TKA requiring explant. The anti-TNF group had 3.26% (3/92) local site infection versus 2.10% (3/143) in the group without anti-TNF and this difference was not statistically significant (Fisher exact test, p = 0.68). The one deep joint infection was in the anti-TNF group. Six-month AE rate was 7.61% in the anti-TNF group versus 6.99% in the group without anti-TNF (Fisher exact test, p = 1.0). There was a low risk of infection and perioperative adverse events in patients with RA receiving anti-TNF therapy who were undergoing TKR. This raises the question whether it is necessary to stop anti-TNF for a long period prior to surgery. Given the possible risks associated with stopping anti-TNF, including worsening of disease, further study is needed to determine optimal perioperative use of anti-TNF among patients with RA undergoing TKR.


Susceptibility of herpes simplex virus type 1 to monoterpenes thymol, carvacrol, p-cymene and essential oils of Sinapis arvensis L., Lallemantia royleana Benth. and Pulicaria vulgaris Gaertn.
In recent years, with increased the prevalence of viral infections and having no specific for their treatment and also the continuous appearance of resistant viral strains, the finding of novel antiviral agents is necessary. In this study, monoterpenes of thymol, carvacrol, p-cymene and essential oils from Sinapis arvensis L., Lallemantia royleana Benth. and Pulicaria vulgaris Gaertn. were screened for their inhibitory effect against herpes simplex virus type 1 (HSV-1) in vitro on Vero cell line CCL-81-ATCC using a plaque reduction assay. The antiviral activity of three monoterpenes (thymol, carvacrol and p-cymene) and three essential oils were evaluated by cytotoxicity assay, direct plaque test. In addition, the modes of antiviral action of these compounds were investigated during the viral infection cycle. Results showed that the inhibitory concentrations (IC50) were determined at 0.002%, 0.037%, >0.1%, 0.035%, 0.018% and 0.001% for thymol, carvacrol, p-cymene, S. arvensis oil, L. royleana oil and P. vulgaris oil, respectively. A manifestly dose-dependent virucidal activity against HSV-1 could be exhibited for compounds tested. In order to determine the mode of the inhibitory effect, compounds were added at different stages during the viral infection cycle. At maximum noncytotoxic concentrations of the compounds, plaque formation was significantly reduced by more than 80% when HSV-1 was preincubated with p-cymene. However, no inhibitory effect could be observed when the compounds were added to the cells prior to infection with HSV-1 or after the adsorption period. These results indicate that compounds affected HSV-1 mostly before adsorption and might interact with the viral envelope. Thymol exhibited a high selectivity index and seems to be a promising candidate for topical therapeutic application as antiviral agent for treatment of herpetic infections.


Association between HIV and subpreputial penile wetness in uncircumcised men in South Africa.
To describe the prevalence and characteristics of subpreputial penile wetness and to investigate the association between current levels of penile wetness and HIV infection. Male attenders at a sexually transmitted infections clinic in Durban, South Africa were enrolled and treated for their presenting sexually transmitted infection complaint. They were asked to return after 14 days when a structured questionnaire was administered, and the degree of wetness of the glans penis and coronal sulcus was assessed clinically. Six hundred and fifty men were enrolled, and 488 (75%) returned. Three hundred eighty-six uncircumcised men were included for statistical analysis of whom 215 (56%) were HIV positive. One hundred ninety-six (50.8%) had no penile wetness, and 190 (49.2%) had penile wetness. In the adjusted analysis, penile wetness was associated with younger age, low level of attained education, low income, higher lifetime numbers of sexual partners, and not washing after sex. The prevalence of HIV was greater in those with penile wetness 126 of 190 (66.3%) compared with 90 of 196 (45.9%) with no penile wetness, crude prevalence odds ratio 2.32 (95% confidence interval [CI], 1.54-3.50, P=or<0.001), crude prevalence relative risk 1.44 (95% CI, 1.23-1.63, P=or<0.001), and adjusted for predictors of HIV, confounders and herpes type 2 antibodies, odds ratio 2.38 (95% CI, 1.42-3.97, P=or<0.001), and relative risk 1.46 (95% CI, 1.19-1.68, P=or<0.001). This is the first study to show an association between subpreputial penile wetness and HIV. Consideration should be given to providing advice about improving penile hygiene in uncircumcised men in areas where HIV is a significant problem. Good penile hygiene should also be promoted at the community level to become a desirable social norm.


Repression of major histocompatibility complex IA expression by glucocorticoids: the glucocorticoid receptor inhibits the DNA binding of the X box DNA binding protein.
Glucocorticoids are effective repressors of major histocompatibility complex (MHC) class II gene expression. The repression occurs in B cells, which constitutively express MHC class II, as well as in macrophages, which only express MHC class II after the cells are treated with interferon gamma. For the MHC class II gene IA beta, this negative regulation has been linked to the X box DNA sequence, located with the IA beta promoter. The addition of the glucocorticoid receptor was shown to inhibit the DNA binding of the X box DNA binding protein to the X box. The DNA binding of two other DNA binding proteins that recognize elements within this promoter was unaffected by the addition of glucocorticoid receptor. It is likely that the repression of IA beta gene expression by glucocorticoids occurs because the X box DNA binding protein is prevented from binding to the DNA and activating transcription.


Robust In Vitro and In Vivo Neutralization against Multiple High-Risk HPV Types Induced by a Thermostable Thioredoxin-L2 Vaccine.
Current prophylactic virus-like particle (VLP) human papillomavirus (HPV) vaccines are based on the L1 major capsid protein and provide robust but virus type-restricted protection. Moreover, VLP vaccines have a high production cost, require cold-chain storage, and are thus not readily implementable in developing countries, which endure 85% of the cervical cancer-related death burden worldwide. In contrast with L1, immunization with minor capsid protein L2 elicits broad cross-neutralization, and we previously showed that insertion of a peptide spanning amino acids 20-38 of L2 into bacterial thioredoxin (Trx) greatly enhances its immunogenicity. Building on this finding, we use, here, four different neutralization assays to demonstrate that low doses of a trivalent Trx-L2 vaccine, incorporating L2(20-38) epitopes from HPV16, HPV31 and HPV51, and formulated in a human-compatible adjuvant, induce broadly protective responses. Specifically, we show that this vaccine, which uses a far-divergent archaebacterial thioredoxin as scaffold and is amenable to an easy one-step thermal purification, induces robust cross-neutralization against 12 of the 13 known oncogenic HPV types. Immune performance measured with two different in vitro neutralization assays was corroborated by the results of mouse cervico-vaginal challenge and passive transfer experiments indicating robust cross-protection also in vivo. Altogether, our results attest to the potential of Trx-L2 as a thermostable second-generation HPV vaccine particularly well suited for low-resource countries.


Structurally designed trans-2-phenylcyclopropylamine derivatives potently inhibit histone demethylase LSD1/KDM1 .
Lysine-specific demethylase 1 (LSD1/KDM1) demethylates histone H3, in addition to tumor suppressor p53 and DNA methyltransferase 1 (Dnmt1), thus regulating eukaryotic gene expression by altering chromatin structure. Specific inhibitors of LSD1 are desired as anticancer agents, because LSD1 aberrations are associated with several cancers, and LSD1 inhibition restores the expression of abnormally silenced genes in cancerous cells. In this study, we designed and synthesized several candidate compounds to inhibit LSD1, based on the structures of LSD1 and monoamine oxidase B (MAO-B), in complex with an antidepressant tranylcypromine (2-PCPA) derivative. Compound S2101 exhibited stronger LSD1 inhibition than tranylcypromine and the known small LSD1 inhibitors in LSD1 demethylation assays, with a k(inact)/K(I) value of 4560 M(-1) s(-1). In comparison with tranylcypromine, the compound displayed weaker inhibition to the monoamine oxidases. The inhibition modes of the two 2-PCPA derivatives, 2-PFPA and S1201, were identified by determination of the inhibitor-bound LSD1 structures, which revealed the enhanced stability of the inhibitor-FAD adducts by their interactions with the surrounding LSD1 residues. These molecules are potential pharmaceutical candidates for cancer or latent virus infection, as well as research tools for LSD1-related biological investigations.


Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne.
The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.


Clinical spectrum of the pseudotumor cerebri in children: etiological, clinical features, treatment and prognosis.
Pseudotumor cerebri (PTC) is a clinical condition characterized by signs and symptoms of increased intracranial pressure, such as headache and papilledema. Our aim was to investigate the etiological and clinical features of pseudotumor cerebri (PTC) in children. We performed a comprehensive analysis of epidemiology, diagnostic work-up, therapy, and clinical follow-up in 42 consecutive patients. Totally 42 patients diagnosed with PTC [27 (64.3%) females and 15 (35.7%) males] were included in the study. The average age of the symptoms onset was 10.79±3.43 years (range from 12 months to 17 years). Obesity was found in eleven (26.2%) of them. Two of the patients had familial mediterranean fever, two of them had posttraumatic PTC. The following diseases were one patient, respectively; mycophenolate mofetil-induced PTC, hypervitaminosis A induced PTC, corticosteroid induced withdrawal due to nephritic syndrome, use of oral contraceptives, Guillain-Barre syndrome, urinary tract infection, varicella-zoster virus infection and dural venous sinus thrombosis associated with otitis media. The most common symptom was headache, recorded in 76.2% of the patients. All patients were treated medically. Three patients in our group also required a ventriculoperitoneal shunt. Pseudotumor cerebri is an avoidable cause of visual loss, both in adults and children. Pre-pubertal obese girls are more common. Medical therapy appeared to be successful in treating pediatric PTC in most patients. Nevertheless, despite adequate treatment, children can rarely experience loss of visual field and acuity; thus, prompt diagnosis and management are important.


Heritability and "environmentability" of electroencephalogram in infants: the twin study.
We estimated relative contribution of genetic and environmental factors to electroencephalogram (EEG) frequency and amplitude parameters in infants. EEG was registered in 49 pairs of monozygotic and 45 pairs of dizygotic twins aged 7-12 months during (1) visual attention and (2) darkness. The variability of occipital alpha frequency depended mainly on genetic, probably nonadditive factors. The mean heritability for the spectral amplitudes in the delta, theta, and alpha bands were 0.37, 0.13, and 0.22 during visual attention, and 0.22, 0.40, and 0.10 during darkness. The influence of shared environment was probable for many of the EEG parameters. It was greatest for the amplitude of the theta rhythm during visual attention. The theta amplitude depended on such a parameter of early social environmental enrichment as the number of caregivers in the family. The possible relationship between infant theta rhythm and developmental outcome is discussed. For many of the EEG parameters, heritability increased during the second half of the first year of life, thus supporting the hypothesis about amplification of genetic effects and decrease of common environmental influences with age.


Optics in du pont.
E. I. du Pont de Nemours, Inc., was founded 170 years ago primarily as a manufacturer of gunpowder. The Company has since diversified into numerous technological areas, and its long list of products now includes many having application in the optics field. In this introduction a brief review of past Du Pont optics work is given.


Assessment of Duguetia furfuracea genotoxic and cytotoxic activity in bacteria and mice.
Duguetia furfuracea (St. Hil.) Benth & Hook f. (1862), popularly known as "sofre-do-rim-quem-quer" and "araticum-seco", is a shrub of the Annonaceae family that occurs in several regions of Brazil. In folk medicine the infusion of its leaves and twigs is used to treat rheumatism and renal colic, whereas the seed powder is mixed with water to treat pediculosis. Previous studies have described biological activities of this plant with cytotoxic, antitumoral, trypanocidal, leishmanicidal, antiplasmodial and antiprotozoal effects. In the present work, genotoxicity and cytotoxicity of Duguetia furfuracea lyophilized leaf extract were evaluated using the prophage λ induction test (SOS-Inductest) and mouse bone marrow micronucleus test. Our results showed that Duguetia furfuracea lyophilized leaf extract did not present an increase either in the induction of prophage λ (P>0.05) using the SOS-inductest or in the micronucleated polychromatic erythrocytes (P>0.05) using the micronucleus test, suggesting absence of genotoxicity in both tests. On the other hand, a significant decrease in the number of bacteria, (P<0.05), as well as a significant decrease in the polychromatic erythrocytes and normochromatic erythrocytes ratio, (P<0.05), were observed, showing the cytotoxic action of Duguetia furfuracea lyophilized leaf extract. Thus, Duguetia furfuracea did not present the genotoxic action, but showed a cytotoxic effect in both assays utilized in the present work.


Can food banks sustain nutrient requirements? A case study in Southwestern Ontario.
Concerns about adequate food supply is a mounting problem in Canada, making food bank visits a necessity for over 820,000 Canadians. Given this reliance, the purpose of this study was to compare contents of food hampers with Canadian guidelines, at a large urban food bank in Southwestern Ontario that intends to provide 3 days worth of food per person. Thirty hampers of each available size (for 1-6 people) were sampled (N = 180). Food items were recorded and analyzed for caloric value, food group, and macro- and micro-nutrient values. Results were compared to Dietary Reference Intakes (DRI) and Canada's Food Guide to Healthy Eating. 99% of hampers did not provide 3 days worth of nutrients. Grains and cereals met the lower range of Canada's Food Guide recommendations, and fruits and vegetables, meats and alternatives, and dairy products were below recommended levels, as were numerous vitamins and minerals, including vitamins A, D, B12, C, riboflavin, niacin, calcium, magnesium and zinc. Carbohydrates were slightly above recommended DRI, and energy from fat and protein scarcely met the minimums recommended. Hampers contained 1.6 days worth of energy per person. The energy available per person was below recommendations for most Canadians. Nutrients missing from the hampers can come from fresh fruits, vegetables, dairy products, and meats and alternatives. However, many low-income families have limited finances to purchase these foods which are relatively more expensive than processed foods. Encouraging more perishable food donations and storage facilities to maximize the nutritional intake for clients is imperative.


Physicochemical properties of double-stranded RNA used to discover a reo-like virus from blue crab Callinectes sapidus.
Mortality among blue crab Callinectes sapidus in soft shell production facilities is typically 25% or greater. The harvest, handling, and husbandry practices of soft shell crab production have the potential to spread or exacerbate infectious crab diseases. To investigate the possible role of viruses in soft shell crab mortalities, we took advantage of the physicochemical properties of double-stranded RNA (dsRNA) to isolate a putative virus genome. Further characterization confirmed the presence of a reo-like virus that possesses 12 dsRNA genome segments. The virus was present in >50% of dead or dying soft shell crabs, but fewer than 5% of healthy hard crabs. Injection of the virus caused mortality and resulted in the appearance of viral RNA and virus inclusions in hemocytes. The genome of the virus was partially sequenced and the information used to develop a reverse transcription polymerase chain reaction (RT-PCR) assay that is able to detect the virus genome in as little as 7.5 pg of total RNA. The molecular tools developed during this study will allow us to quantify prevalence of the blue crab reo-like virus in captive (soft shell facilities, aquaculture operations) and wild populations and facilitate understanding of the role this virus has in blue crab life history.


Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure.
To estimate whether the association between nevirapine (NVP) and hepatotoxicity differs according to pregnancy status in HIV-infected women. The present analysis included HIV-infected pregnant women on antiretroviral therapy (ART) from two multicenter, prospective cohorts - the Women and Infants Transmission Study and the International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1025 - and HIV-infected nonpregnant women from one multicenter, prospective cohort - the Women's Interagency HIV Study. Using multivariate Cox proportional hazards regression, the interaction between NVP and pregnancy status in terms of hepatotoxicity was investigated. NVP use was dichotomized as use or no use and was further categorized according to ART exposure history. We investigated two outcomes: any liver enzyme elevation (LEE; grade 1-4) and severe LEE (grade 3-4). Data on 2050 HIV-infected women taking ART were included: 1229 (60.0%) pregnant and 821 (40.0%) nonpregnant. Among the pregnant women, 174 (14.2%) developed any LEE and 15 (1.2%) developed severe LEE as compared with 75 (9.1%) and 5 (0.6%), respectively, of the nonpregnant women. In multivariate adjusted models, NVP was not significantly associated with risk of LEE, regardless of pregnancy status; however, pregnancy was associated with an increased risk of any LEE (relative risk 4.7, confidence interval = 3.4-6.5) and severe LEE (relative risk 3.8, confidence interval = 1.3-11.1). The association of pregnancy and LEE was seen, regardless of prior ART and NVP exposure history. No significant association between NVP and LEE was observed, regardless of pregnancy status, but pregnancy was significantly associated with increased hepatotoxocity in HIV-infected women.


The role of membrane lipids in the induction of macrophage apoptosis by microparticles.
Microparticles are membrane-derived vesicles that are released from cells during activation or cell death. These particles can serve as mediators of intercellular cross-talk and induce a variety of cellular responses. Previous studies have shown that macrophages undergo apoptosis after phagocytosing microparticles. Here, we have addressed the hypothesis that microparticles trigger this process via lipid pathways. In these experiments, microparticles induced apoptosis in primary macrophage cells or cell lines (RAW 264.7 or U937) with up to a 5-fold increase. Preincubation of macrophages with phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)BP) reduced the microparticle-induced apoptosis in a dose-dependent manner. PtdIns(3,5)BP is a specific inhibitor of the acid sphingomyelinase and thus can block the generation of pro-apoptotic ceramides. Similarly, the pre-incubation of macrophages with PtdIns(3,5)BP prevented microparticle-induced upregulation of caspase 8, which is a major target molecule of ceramide action in the apoptosis pathway. PtdIns(3,5)BP, however, had no effect on the spontaneous rate of apoptosis. To evaluate further signaling pathways induced by microparticles, the extracellular signal regulated kinase (ERK-) 1 was investigated. This kinase plays a role in activating phospholipases A2 which cleaves membrane phospholipids into arachidonic acid; microparticles have been suggested to be a preferred substrate for phospholipases A2. As shown in our experiments, microparticles strongly increased the amount of phosphorylated ERK1/2 in RAW 264.7 macrophages in a time-dependent manner, peaking 15 min after co-incubation. Addition of PD98059, a specific inhibitor of ERK1, prevented the increase in apoptosis of RAW 264.7 macrophages. Together, these data suggest that microparticles perturb lipid homeostasis of macrophages and thereby induce apoptosis. These results emphasize the importance of biolipids in the cellular cross-talk of immune cells. Based on the fact that in clinical situations with excessive cell death such as malignancies, autoimmune diseases and following chemotherapies high levels of circulating microparticles might modulate phagocytosing cells, a suppression of the immune response might occur due to loss of macrophages.


REMOTE, a Wireless Sensor Network Based System to Monitor Rowing Performance.
In this paper, we take a hard look at the performance of REMOTE, a sensor network based application that provides a detailed picture of a boat movement, individual rower performance, or his/her performance compared with other crew members. The application analyzes data gathered with a WSN strategically deployed over a boat to obtain information on the boat and oar movements. Functionalities of REMOTE are compared to those of RowX [1] outdoor instrument, a commercial wired sensor instrument designed for similar purposes. This study demonstrates that with smart geometrical configuration of the sensors, rotation and translation of the oars and boat can be obtained. Three different tests are performed: laboratory calibration allows us to become familiar with the accelerometer readings and validate the theory, ergometer tests which help us to set the acquisition parameters, and on boat tests shows the application potential of this technologies in sports.


Prenatal phthalate exposures and anogenital distance in Swedish boys.
Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and in a large number of consumer products. Because of reported health risks, diisononyl phthalate (DiNP) has been introduced as a replacement for di(2-ethylhexyl) phthalate (DEHP) in soft PVC. This raises concerns because animal data suggest that DiNP may have antiandrogenic properties similar to those of DEHP. The anogenital distance (AGD)--the distance from the anus to the genitals--has been used to assess reproductive toxicity. The objective of this study was to examine the associations between prenatal phthalate exposure and AGD in Swedish infants. AGD was measured in 196 boys at 21 months of age, and first-trimester urine was analyzed for 10 phthalate metabolites of DEP (diethyl phthalate), DBP (dibutyl phthalate), DEHP, BBzP (benzylbutyl phthalate), as well as DiNP and creatinine. Data on covariates were collected by questionnaires. The most significant associations were found between the shorter of two AGD measures (anoscrotal distance; AGDas) and DiNP metabolites and strongest for oh-MMeOP [mono-(4-methyl-7-hydroxyloctyl) phthalate] and oxo-MMeOP [mono-(2-ethyl-5-oxohexyl) phthalate]. However, the AGDas reduction was small (4%) in relation to more than an interquartile range increase in DiNP exposure. These findings call into question the safety of substituting DiNP for DEHP in soft PVC, particularly because a shorter male AGD has been shown to relate to male genital birth defects in children and impaired reproductive function in adult males and the fact that human levels of DiNP are increasing globally.


Clinical and demographic characteristics related to onset site and spread of cervical dystonia.
Clinical characteristics of isolated idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. The objectives of this study were to characterize the clinical characteristics and demographics of isolated idiopathic cervical dystonia in the largest standardized multicenter cohort. The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe, and Australia, recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread. Site of dystonia onset was: (1) focal neck only (78.5%), (2) focal onset elsewhere with later segmental spread to neck (13.3%), and (3) segmental onset with initial neck involvement (8.2%). Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than the 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, was associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age. Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. © 2016 International Parkinson and Movement Disorder Society.


Molecular imaging probes for multi-spectral optoacoustic tomography.
Multi-Spectral Optoacoustic Tomography (MSOT) merges the power of high-resolution imaging at tissue depths of several millimeters to centimeters with the advantages of optical imaging, in large part by exploiting spectral detection of endogenous molecules in tissue or exogenous photoabsorbing probes. Current advances in fast-tuning laser technology, image reconstruction and spectral detection schemes have yielded real-time optoacoustic (photoacoustic) imaging spanning applications from microscopy to human imaging. This progress has generated an unprecedented need for imaging probes and reporter gene approaches optimized for optoacoustic signal generation. New classes of probes are emerging and create new opportunities for visualizing morphological and pathophysiological features in vivo, in a non-invasive manner. Here we review recent progress in optoacoustic probes and discuss applications and challenges for biological imaging as well as prospects for clinical translation.


Surfactant protein-A and phosphatidylglycerol suppress type IIA phospholipase A2 synthesis via nuclear factor-kappaB.
We previously showed that surfactant inhibits the synthesis of type IIA secretory phospholipase A2 (sPLA2-IIA) by alveolar macrophages. These cells have been identified as the main source of this enzyme in an animal model of acute lung injury. The aim of the present study was to identify the surfactant components involved in the inhibition of sPLA2-IIA expression in alveolar macrophages and the signaling pathways that mediate this inhibition. Our results show that various surfactant preparations can inhibit sPLA2-IIA expression in endotoxin-stimulated alveolar macrophages. Both the surfactant protein (SP)-A and the surfactant phospholipid fraction inhibit this expression. The surfactant phospholipid dioleylphosphatidylglycerol (DOPG) abolishes sPLA2-IIA expression, whereas dipalmitoylphosphatidylcholine does not. Chromatographic analysis and confocal microscopy revealed that phosphatidylglycerol was rapidly incorporated and metabolized by alveolar macrophages and that its metabolites accumulate in the cytosol. Nuclear factor-kappaB (NF-kappaB) modulates sPLA2-IIA expression in endotoxin-activated alveolar macrophages, and surfactant preparations, surfactant phospholipid fraction, SP-A, and DOPG indeed suppressed NF-kappaB activation. In summary, our results show that SP-A and DOPG play a role in the surfactant-mediated inhibition of sPLA2-IIA expression in alveolar macrophages and that this inhibition occurs via a downregulation of NF-kappaB activation.


Saccharomyces boulardii ameliorates Citrobacter rodentium-induced colitis through actions on bacterial virulence factors.
Saccharomyces boulardii has received increasing attention as a probiotic effective in the prevention and treatment of infectious and inflammatory bowel diseases. The aim of this study was to examine the ameliorating effects of S. boulardii on Citrobacter rodentium colitis in vivo and identify potential mechanisms of action. C57BL/6 mice received 2.5 x 10(8) C. rodentium by gavage on day 0, followed by S. boulardii (25 mg; 5 x 10(8) live cells) gavaged twice daily from day 2 to day 9. Animal weights were monitored until death on day 10. Colons were removed and assessed for epithelial barrier function, histology, and myeloperoxidase activity. Bacterial epithelial attachment and type III secreted proteins translocated intimin receptor Tir (the receptor for bacterial intimin) and EspB (a translocation apparatus protein) required for bacterial virulence were assayed. In infected mice, S. boulardii treatment significantly attenuated weight loss, ameliorated crypt hyperplasia (234.7 +/- 7.2 vs. 297.8 +/- 17.6 microm) and histological damage score (0.67 +/- 0.67 vs. 4.75 +/- 0.75), reduced myeloperoxidase activity (2.1 +/- 0.4 vs. 4.7 +/- 0.9 U/mg), and attenuated increased mannitol flux (17.2 +/- 5.0 vs. 31.2 +/- 8.2 nm.cm(-2).h(-1)). The ameliorating effects of S. boulardii were associated with significantly reduced numbers of mucosal adherent C. rodentium, a marked reduction in Tir protein secretion and translocation into mouse colonocytes, and a striking reduction in EspB expression and secretion. We conclude that S. boulardii maintained colonic epithelial barrier integrity and ameliorated inflammatory sequelae associated with C. rodentium infection by attenuating C. rodentium adherence to host epithelial cells through putative actions on the type III secretion system.


Transitions from near-surface to interior redox upon lithiation in conversion electrode materials.
Nanoparticle electrodes in lithium-ion batteries have both near-surface and interior contributions to their redox capacity, each with distinct rate capabilities. Using combined electron microscopy, synchrotron X-ray methods and ab initio calculations, we have investigated the lithiation pathways that occur in NiO electrodes. We find that the near-surface electroactive (Ni(2+) → Ni(0)) sites saturated very quickly, and then encounter unexpected difficulty in propagating the phase transition into the electrode (referred to as a "shrinking-core" mode). However, the interior capacity for Ni(2+) → Ni(0) can be accessed efficiently following the nucleation of lithiation "fingers" that propagate into the sample bulk, but only after a certain incubation time. Our microstructural observations of the transition from a slow shrinking-core mode to a faster lithiation finger mode corroborate with synchrotron characterization of large-format batteries and can be rationalized by stress effects on transport at high-rate discharge. The finite incubation time of the lithiation fingers sets the intrinsic limitation for the rate capability (and thus the power) of NiO for electrochemical energy storage devices. The present work unravels the link between the nanoscale reaction pathways and the C-rate-dependent capacity loss and provides guidance for the further design of battery materials that favors high C-rate charging.


Temporal Trends and Outcomes of Patients Undergoing Percutaneous Coronary Interventions for Cardiogenic Shock in the Setting of Acute Myocardial Infarction: A Report From the CathPCI Registry.
The purpose of this study was to examine the temporal trends in demographics, clinical characteristics, management strategies, and in-hospital outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (CS-AMI) who underwent percutaneous coronary intervention (PCI) from the Cath-PCI Registry (2005 to 2013). The authors examined contemporary use and outcomes of PCI in patients with CS-AMI. The authors used the Cath-PCI Registry to evaluate 56,497 patients (January 2005 to December 2013) undergoing PCI for CS-AMI. Temporal trends in clinical variables and outcomes were assessed. Compared with cases performed from 2005 to 2006, CS-AMI patients receiving PCI from 2011 to 2013 were more likely to have diabetes, hypertension, dyslipidemia, previous PCI, dialysis, but less likely to have chronic lung disease, peripheral vascular disease, or heart failure within 2 weeks (p < 0.01). Between 2005 and 2006 to 2011 and 2013, intra-aortic balloon pump use decreased (49.5% to 44.9%; p < 0.01), drug-eluting stent use declined (65% to 46%; p < 0.01), and the use of bivalirudin increased (12.6% to 45.6%). Adjusted in-hospital mortality; increased (27.6% in 2005 to 2006 vs. 30.6% in 2011 to 2013, adjusted odds ratio: 1.09, 95% confidence interval: 1.005 to .173; p = 0.04) for patients who were managed with an early invasive strategy (<24 h from symptoms). Our study shows that despite the evolution of medical technology and use of contemporary therapeutic measures, in-hospital mortality in CS-AMI patients who are managed invasively continues to rise. Additional research and targeted efforts are indicated to improve outcomes in this high-risk cohort.


Medicinal plants and dementia therapy: herbal hopes for brain aging?
An escalating "epidemic" of diseases like Alzheimer's has not yet been met by effective symptomatic treatments or preventative strategies. Among a few current prescription drugs are cholinesterase inhibitors including galantamine, originating from the snowdrop. Research into ethnobotanicals for memory or cognition has burgeoned in recent years. Based on a multi-faceted review of medicinal plants or phytochemicals, including traditional uses, relevant bioactivities, psychological and clinical evidence on efficacy and safety, this overview focuses on those for which there is promising clinical trial evidence in people with dementia, together with at least one other of these lines of supporting evidence. With respect to cognitive function, such plants reviewed include sage, Ginkgo biloba, and complex mixtures of other traditional remedies. Behavioral and psychological symptoms of dementia (BPSD) challenge carers and lead to institutionalization. Symptoms can be alleviated by some plant species (e.g., lemon balm and lavender alleviate agitation in people with dementia; St John's wort treats depression in the normal population). The ultimate goal of disease prevention is considered from the perspective of limited epidemiological and clinical trial evidence to date. The potential value of numerous plant extracts or chemicals (e.g., curcumin) with neuroprotective but as yet no clinical data are reviewed. Given intense clinical need and carer concerns, which lead to exploration of such alternatives as herbal medicines, the following research priorities are indicated: investigating botanical agents which enhance cognition in populations with mild memory impairment or at earliest disease stages, and those for BPSD in people with dementia at more advanced stages; establishing an ongoing authoritative database on herbal medicine for dementia; and further epidemiological and follow up studies of promising phytopharmaceuticals or related nutraceuticals for disease prevention.


Tissue morphogenesis and vascular stability require the Frem2 protein, product of the mouse myelencephalic blebs gene.
Adhesive properties of cells undergoing morphogenetic rearrangements can be regulated either at the cellular level or by altering the environment in which rearrangements occur. Here, we describe the identification of a mutation (my(F11)) in the mouse extracellular matrix component Frem2, and provide evidence that suggests Frem2 expression creates an environment conducive to morphogenetic events. Loss of Frem2 function results in defects in developmental events associated with morphogenetic rearrangements of the vasculature and of tissues arising from all germ layers. The Frem2 transcript is restricted both spatially and temporally and appears in advance of cell rearrangement events. Thus, expression of Frem2 may dynamically alter the extracellular matrix to provide a substrate for cell migration and rearrangements during embryogenesis.


Impact of capsular switch on invasive pneumococcal disease incidence in a vaccinated population.
Despite the dramatic decline in the incidence of invasive pneumococcal disease (IPD) observed since the introduction of conjugate vaccination, it is feared that several factors may undermine the future effectiveness of the vaccines. In particular, pathogenic pneumococci may switch their capsular types and evade vaccine-conferred immunity. Here, we first review the literature and summarize the available epidemiological data on capsular switch for S. pneumoniae. We estimate the weekly probability that a persistently carried strain may switch its capsule from four studies, totalling 516 children and 6 years of follow-up, at 1.5x10(-3)/week [4.6x10(-5)-4.8x10(-3)/week]. There is not enough power to assess an increase in this frequency in vaccinated individuals. Then, we use a mathematical model of pneumococcal transmission to quantify the impact of capsular switch on the incidence of IPD in a vaccinated population. In this model, we investigate a wide range of values for the frequency of vaccine-selected capsular switch. Predictions show that, with vaccine-independent switching only, IPD incidence in children should be down by 48% 5 years after the introduction of the vaccine with high coverage. Introducing vaccine-selected capsular switch at a frequency up to 0.01/week shows little effect on this decrease; yearly, at most 3 excess cases of IPD per 10(6) children might occur due to switched pneumococcal strains. Based on all available data and model predictions, the existence of capsular switch by itself should not impact significantly the efficacy of pneumococcal conjugate vaccination on IPD incidence. This optimistic result should be tempered by the fact that the selective pressure induced by the vaccine is currently increasing along with vaccine coverage worldwide; continued surveillance of pneumococcal populations remains of the utmost importance, in particular during clinical trials of the new conjugate vaccines.


Prenatal exposure to organophosphate pesticides and reciprocal social behavior in childhood.
Prenatal exposure to organophosphate pesticides (OPs) has been associated with adverse neurodevelopmental outcomes in childhood, including low IQ, pervasive developmental disorder (PDD), attention problems and ADHD. Many of these disorders involve impairments in social functioning. Thus, we investigated the relationship between biomarkers of prenatal OP exposure and impaired reciprocal social behavior in childhood, as measured by the Social Responsiveness Scale (SRS). Using a multi-ethnic urban prospective cohort of mother-infant pairs in New York City recruited between 1998 and 2002 (n=404) we examined the relation between third trimester maternal urinary levels of dialkylphosphate (ΣDAP) OP metabolites and SRS scores among 136 children who returned for the 7-9year visit. Overall, there was no association between OPs and SRS scores, although in multivariate adjusted models, associations were heterogeneous by race and by sex. Among blacks, each 10-fold increase in total diethylphosphates (ΣDEP) was associated with poorer social responsiveness (β=5.1 points, 95% confidence interval (CI) 0.8, 9.4). There was no association among whites or Hispanics, or for total ΣDAP or total dimethylphosphate (ΣDMP) biomarker levels. Additionally, stratum-specific models supported a stronger negative association among boys for ΣDEPs (β=3.5 points, 95% CI 0.2, 6.8), with no notable association among girls. Our results support an association of prenatal OP exposure with deficits in social functioning among blacks and among boys, although this may be in part reflective of differences in exposure patterns.


Homologation of halostannanes with carbenoids: a convenient and straightforward one-step access to α-functionalized organotin reagents.
A direct, single synthetic homologative transformation of halostannanes into mono- or di-substituted methyl analogues is documented. Critical for the success of the operation is the excellent nucleophilicity of carbenoid-like methyllithium reagents (LiCHXY, X, Y = halogen, OR, and CN): by simply individuating the reagents' substitution pattern, the desired functionalized fragment is delivered to the electrophile. The wide scope of the protocol is evidenced also in the case of analogous halogermanium compounds. The tandem homologation-quenching with nucleophiles and the use of α-chloroallyllithium is also discussed.


Emerging therapies for pancreas neuroendocrine cancers.
Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors can be functional, i.e., hormone secreting tumors, e.g., insulinoma, gastrinoma or VIPoma, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNET's, usually present later either incidentally or due to tumor bulk symptoms. The recent WHO classification system in 2010 classified PNET's into different stages and grades depending on the mitotic activity and Ki-67 labeling index. PNET's have a broad range of prognoses depending on the histologic grade, differentiation and biologic behavior. Computerized tomographic scanning (CT), magnetic resonance imaging (MRI) and octreoscan are imaging tools used to diagnose PNET, in addition to a confirmatory tissue diagnosis with immunohistochemical stains, typically obtained by either cytologic or histologic assessment. Symptomatic advanced PNET's can be treated with a long-acting somatostatin analogue for those tumors with somatostatin receptor positivity and which may also have antiproliferative activity. Another treatment modality is peptide receptor radionucleotide therapy (PRRT) in somatostatin receptor-positive tumors, albeit as yet with limited availability in the United States. Systemic therapies with combination cytotoxic agents e.g., streptozocin, anthracyclines, and capecitabine and temozolomide, all have established activity in PNET's. Biologic agents targeting the VEGF and mTOR signaling pathways, e.g., sunitinib, bevacizumab or everolimus are becoming integrated as treatments for PNET's. Poorly differentiated, high grade PNETs with a very high mitotic rate are treated with platinum-based chemotherapy regimens similar to treatment paradigms for small cell carcinoma of the lung. For liver confined or predominant disease, strategies such as cytoreductive surgery, hepatic artery embolization or radioembolization are treatment modalities to effect locoregional tumor control. The next generation of studies in PNET will help define optimal sequencing strategies of available therapies and also will attempt to use biomarker-guided approaches to select therapies.


Investigation of the methylerythritol 4-phosphate pathway for microbial terpenoid production through metabolic control analysis.
Terpenoids are of high interest as chemical building blocks and pharmaceuticals. In microbes, terpenoids can be synthesized via the methylerythritol phosphate (MEP) or mevalonate (MVA) pathways. Although the MEP pathway has a higher theoretical yield, metabolic engineering has met with little success because the regulation of the pathway is poorly understood. We applied metabolic control analysis to the MEP pathway in Escherichia coli expressing a heterologous isoprene synthase gene (ispS). The expression of ispS led to the accumulation of isopentenyl pyrophosphate (IPP)/dimethylallyl pyrophosphate (DMAPP) and severely impaired bacterial growth, but the coexpression of ispS and isopentenyl diphosphate isomerase (idi) restored normal growth and wild-type IPP/DMAPP levels. Targeted proteomics and metabolomics analysis provided a quantitative description of the pathway, which was perturbed by randomizing the ribosome binding site in the gene encoding 1-deoxyxylulose 5-phosphate synthase (Dxs). Dxs has a flux control coefficient of 0.35 (i.e., a 1% increase in Dxs activity resulted in a 0.35% increase in pathway flux) in the isoprene-producing strain and therefore exerted significant control over the flux though the MEP pathway. At higher dxs expression levels, the intracellular concentration of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEcPP) increased substantially in contrast to the other MEP pathway intermediates, which were linearly dependent on the abundance of Dxs. This indicates that 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (IspG), which consumes MEcPP, became saturated and therefore limited the flux towards isoprene. The higher intracellular concentrations of MEcPP led to the efflux of this intermediate into the growth medium. These findings show the importance of Dxs, Idi and IspG and metabolite export for metabolic engineering of the MEP pathway and will facilitate further approaches for the microbial production of valuable isoprenoids.


The role of vision and spatial orientation in the maintenance of posture.
This article reviews and analyzes the role of vision and spatial orientation in maintaining posture and balance. The key issues that relate to the development of postural control across the life span are discussed. Use of vision as a critical source of information that specifies spatial orientation in the environment is considered. We argue that the visual system functions as part of the perception-action cycle as promoted in ecological psychology by James Gibson. We compare and contrast theory and evidence of both standard and ecological accounts of how the visual system perceives the information and the findings relative to the role of the retinal vision in processing and acting on information related to motion. Changes in the ambient optical array (optical flow) as a non-force field are compared with gravity-based perturbations relative to the possible influence of the non-force field to changes in the motor system. Finally, a summary of some of our own work is presented, with comments about implications for further research and possible applications to clinical practice.


Absolute change in fasting plasma glucose over 12 months is associated with 2-year and 5-year major adverse cardiovascular events in patients with drug-eluting stent implants.
Major adverse cardiovascular events (MACEs) in patients with or without cardiovascular disease (CVD) are greatly affected by various factors associated with metabolism and inflammation. To determine which clinical parameters at treatment are associated with the development of 2-year and 5-year MACEs in high-risk patients with CVD who have undergone drug-eluting stent (DES) implantation. The present study involved a total of 432 patients who underwent percutaneous coronary intervention with DES. Variables representing the average and absolute amount of change in clinical parameters over the 12-month follow-up were assessed for association with 2-year and 5-year development of MACE. The study population was divided into quartiles for the variable showing the highest correlation to MACE development. Estimated incidence of 2-year and 5-year MACEs for each of the quartiles was determined by survival curve analysis, and subgroup analysis was performed for patients with diabetes and statin users. Absolute change in fasting plasma glucose (FPG) over 12 months showed the highest correlation with 2-year and 5-year MACE development. The estimated incidence of MACE increased with increasing quartiles for absolute change in FPG. The association between absolute change in FPG and MACE development exhibited a stronger relationship for the specific subgroups of patients with diabetes and statin users. Increases and decreases in FPG had a comparable contribution to MACE development. A greater absolute change in FPG over 12 months post-PCI is an independent risk factor for 2-year and 5-year MACE development in DES-implanted patients, especially in the diabetes and statin users.


Transforming growth factor beta is a major regulator of human neonatal immune responses following respiratory syncytial virus infection.
Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T-cell responses may contribute to RSV immunopathology, which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the lungs with a decrease in the blood. Pediatric populations are particularly susceptible to severe RSV infections; however, DC responses to RSV from pediatric populations have not been examined. In this study, primary isolated DCs from cord blood and adult peripheral blood were compared after RSV infection. Transcriptional profiling and biological network analysis identified transforming growth factor beta (TGF-β) and associated signaling molecules as differentially regulated in the two age groups. TGF-β1 was decreased in RSV-infected adult-blood DCs but increased in RSV-infected cord blood DCs. Coculture of adult RSV-infected DCs with autologous T cells induced secretion of gamma interferon (IFN-γ), interleukin 12p70 (IL-12p70), IL-2, and tumor necrosis factor alpha (TNF-α). Conversely, coculture of cord RSV-infected DCs and autologous T cells induced secretion of IL-4, IL-6, IL-1β, and IL-17. Addition of purified TGF-β1 to adult DC-T-cell cocultures reduced secretion of IFN-γ, IL-12p70, IL-2, and TNF-α, while addition of a TGF-β chemical inhibitor to cord DC-T-cell cocultures increased secretion of IL-12p70. These data suggest that TGF-β acts as a major regulator of RSV DC-T-cell responses, which could contribute to immunopathology during infancy.


The Depressive Attributions Questionnaire (DAQ): Development of a Short Self-Report Measure of Depressogenic Attributions.
A depressogenic attributional style, i.e., internal, stable and global causal interpretations of negative events, is a stable vulnerability factor for depression. Current measures of pessimistic attributional style can be time-consuming to complete, and some are designed for specific use with student populations. We developed and validated a new short questionnaire suitable for the measurement of depressogenic attributions in clinical settings, the Depressive Attributions Questionnaire (DAQ). The 16-item DAQ, and measures of depression and related cognitive concepts were completed by three samples of depressed patients and matched controls, or depressed and non-depressed participants who had been exposed to a recent uncontrollable stressful life event (total N = 375). The DAQ had high (i) internal reliability, (ii) test-retest reliability, (iii) convergent, discriminant and construct validity. It predicted a diagnosis of major depression at 6 months after an uncontrollable stressor, over and above what could be predicted from initial depression severity. Depressed patients rated the scale as acceptable. The DAQ may be a useful short measure of depressogenic attributions, which is easy to administer, and predicts concurrent and future depression. It has possible applications as a screening measure for risk of depression, or as a treatment process measure.


Probing the spinor nature of electronic states in nanosize non-collinear magnets.
Non-collinear magnetization textures provide a route to novel device concepts in spintronics. These applications require laterally confined non-collinear magnets (NCM). A crucial aspect for potential applications is how the spatial proximity between the NCM and vacuum or another material impacts the magnetization texture on the nanoscale. We focus on a prototypical exchange-driven NCM given by the helical spin order of bilayer Fe on Cu(111). Spin-polarized scanning tunnelling spectroscopy and density functional theory reveal a nanosize- and proximity-driven modification of the electronic and magnetic structure of the NCM in interfacial contact with a ferromagnet or with vacuum. An intriguing non-collinearity between the local magnetization in the sample and the electronic magnetization probed above its surface results. It is a direct consequence of the spinor nature of electronic states in NCM. Our findings provide a possible route for advanced control of nanoscale spin textures by confinement.


AChE-rich magnopyramidal neurons have a left-right size asymmetry in Broca's area.
Acetylcholinesterase-rich neurons (AChERN) are a particular group of pyramidal neurons, displaying a specific laminar and ontogenetic pattern in the cerebral cortex of human and nonhuman primates. Using histochemistry and morphometrical methods, we have found a layer 3 magnopyramidal AChERN left-right size asymmetry restricted to Brodmann's area 45, a component of Broca's language area. This structural feature could be related to functional lateralization associated to syntactic processing and phonological working memory, and is consistent with a non-cholinergic role of AChE possibly linked to neuroplastic processes in the human neocortex.


Changes in adiposity in an older Chinese population in rapid economic transition.
To examine the changes in body mass index (BMI) and waist circumference (WC) in Guangzhou, South China, which is probably experiencing the most rapid economic transition in history. In this study, 17,786 Chinese aged 50+ years were recruited from 2003 to 2008 and followed up until 2012. BMI and WC were measured at two time points. During the mean follow-up of 3.6 years (median = 3, interquartile = 1), age-adjusted mean BMI increased only slightly. By contrast, mean WC increased sharply by 0.94 cm (95% confidence interval 0.93-0.94) annually in men and 1.29 cm (1.28-1.29) annually in women. In 77% of women and 69% of men, WC increased, and among them, the mean annual increase was 2.01 cm and 1.70 cm, respectively. Among healthy, never-smoking participants, the incidence of central obesity was 29.0% (36.4% in women and 14.2% in men). The incidence of general obesity was 1.9% and was similarly low in both men and women (2.1% vs. 1.8%). Conversely, 20.3% of individuals with general obesity became nonobese, and 12.8% of individuals with central obesity returned to normal. Central obesity has risen sharply in this cohort. Such increases may have been greatly underestimated previously and should form the basis of an even stronger warning for regions undergoing economic transitions in China and elsewhere.


Effect of prenatal steroid treatment on the developing immune system.
Prenatal steroids have an undisputed positive effect of decreasing neonatal morbidity and mortality by improving fetal lung maturation. Some concerns have been raised on long-term consequences on the hypothalamic-pituitary-adrenal axis and cognition, but there are no studies addressing effects on the immune system. The thymus is an essential organ for the development and selection of T cells, and thymocytes are extremely sensitive to steroids. Using a mouse model for prenatal steroid administration, we show here that betamethasone treatment to the mother has a profound effect on the thymus of the offspring. We find the thymus volume reduced, affecting mostly the developing CD4+ CD8+ double-positive thymocytes and a compensatory accelerated transition of the earlier stages to replenish the depleted compartment. This effect lasts for at least 3 days, which correspond to a very relevant period for the selection of the T cell repertoire. Moreover, we show that low doses of betamethasone have similar effects on human thymocytes in vitro. Therefore, further studies are needed to analyze possible long-term consequences of this treatment on the immune system of the offspring. Betamethasone administered to the mother before birth reaches the fetal thymus. Prenatal betamethasone results in massive loss of developing thymocytes. The effects of betamethasone on thymus development are visible for several days. Human thymocytes are also sensitive to low doses of betamethasone. Altered thymocyte development around birth may have an effect on the immune system.


Clinicoradiological Correlation of Infarct Patterns on Diffusion-weighted Magnetic Resonance Imaging in Stroke.
Diffusion-weighted magnetic resonance imaging (DW-MRI) represents a major advance in the early diagnosis of acute ischemic stroke. It can detect edema due to ischemia in the brain tissue. It not only establishes the presence and location of ischemic brain injury but also a relatively new concept is the determination of infarct patterns seen on diffusion imaging and its clinical correlation. Objective To determine the frequency of various infarct patterns and their relationship with functional outcome of the patient. Materials and methods A total of 108 patients with acute stroke were enrolled by purposive sampling. Magnetic resonance imaging (MRI) was obtained with departmental protocol and diffusion-weighted sequences. The clinical data was collected from medical records and functional outcome was assessed at the time of admission using Barthel Index (BI) which was dichotomized into poor and favorable outcomes. The radiological data was collected and three infarct patterns (cortical, subcortical, and territorial infarcts) were recorded from diffusion-weighted images. Association of other risk factors such as age, gender, diabetes, hypertension (HTN), hyperlipidemia, and smoking were also evaluated. Results Amongst the three infarct patterns, subcortical infarcts were noted with the highest proportion of 62% (67/108). The highest proportion of territorial infarcts (78.6%) was significantly associated with a poor outcome in comparison to cortical and subcortical infarcts. Cortical infarcts (61.5%) were significantly associated with good outcomes followed by subcortical and then territorial infarcts (p-value < 0.002). Amongst the risk factors, HTN was found to be highly prevalent followed by diabetes mellitus (DM). Conclusion Subcortical infarct pattern was the most common, followed by territorial and cortical infarct. The highest proportion of infarct pattern with good outcomes was seen with cortical infarcts followed by subcortical and then territorial infarct pattern. HTN and coronary artery disease (CAD) were the effect modifiers showing significant association with poor outcomes.


Phase-gradient algorithm as an optimal estimator of the phase derivative.
The phase-gradient algorithm represents a powerful new signal-processing technique with applications to aperture-synthesis imaging. These include, for example, synthetic-aperture-radar phase correction and stellar-image reconstruction. The algorithm combines redundant information present in the data to arrive at an estimate of the phase derivative. We show that the estimator is in fact a linear, minimum-variance estimator of the phase derivative.