Evaluating contextual processing in diffusion MRI: application to optic radiation reconstruction for epilepsy surgery.
Diffusion MRI and tractography allow for investigation of the architectural configuration of white matter in vivo, offering new avenues for applications like presurgical planning. Despite the promising outlook, there are many pitfalls that complicate its use for (clinical) application. Amongst these are inaccuracies in the geometry of the diffusion profiles on which tractography is based, and poor alignment with neighboring profiles. Recently developed contextual processing techniques, including enhancement and well-posed geometric sharpening, have shown to result in sharper and better aligned diffusion profiles. However, the research that has been conducted up to now is mainly of theoretical nature, and so far these techniques have only been evaluated by visual inspection of the diffusion profiles. In this work, the method is evaluated in a clinically relevant application: the reconstruction of the optic radiation for epilepsy surgery. For this evaluation we have developed a framework in which we incorporate a novel scoring procedure for individual pathways. We demonstrate that, using enhancement and sharpening, the extraction of an anatomically plausible reconstruction of the optic radiation from a large amount of probabilistic pathways is greatly improved in three healthy controls, where currently used methods fail to do so. Furthermore, challenging reconstructions of the optic radiation in three epilepsy surgery candidates with extensive brain lesions demonstrate that it is beneficial to integrate these methods in surgical planning.


EEG Analytics for Early Detection of Autism Spectrum Disorder: A data-driven approach.
Autism spectrum disorder (ASD) is a complex and heterogeneous disorder, diagnosed on the basis of behavioral symptoms during the second year of life or later. Finding scalable biomarkers for early detection is challenging because of the variability in presentation of the disorder and the need for simple measurements that could be implemented routinely during well-baby checkups. EEG is a relatively easy-to-use, low cost brain measurement tool that is being increasingly explored as a potential clinical tool for monitoring atypical brain development. EEG measurements were collected from 99 infants with an older sibling diagnosed with ASD, and 89 low risk controls, beginning at 3 months of age and continuing until 36 months of age. Nonlinear features were computed from EEG signals and used as input to statistical learning methods. Prediction of the clinical diagnostic outcome of ASD or not ASD was highly accurate when using EEG measurements from as early as 3 months of age. Specificity, sensitivity and PPV were high, exceeding 95% at some ages. Prediction of ADOS calibrated severity scores for all infants in the study using only EEG data taken as early as 3 months of age was strongly correlated with the actual measured scores. This suggests that useful digital biomarkers might be extracted from EEG measurements.


Online Health Information Tool Effectiveness for Older Patients: A Systematic Review of the Literature.
Online health information tools (OHITs) have been found to be effective in improving health outcomes. However, the effectiveness of these tools for older patients has been far from clear. This systematic literature review therefore provides an overview of online health information tool effectiveness for older patients using a two-dimensional framework of OHIT functions (i.e., providing information, enhancing information exchange, and promoting self-management) and outcomes (i.e., immediate, intermediate, and long-term outcomes). Comprehensive searches of the PubMed, EMBASE, and PsycINFO databases are conducted to identify eligible studies. Articles describing outcomes of patient-directed OHITs in which a mean sample or subgroup of age ≥65 years was used are included in the literature review. A best evidence synthesis analysis provides evidence that OHITs improve self-efficacy, blood pressure, hemoglobin levels, and cholesterol levels. Limited evidence is found in support of OHIT effects on knowledge, perceived social support, health service utilization, glycemic control, self-care adherence, exercise performance, endurance, and quality of life. OHITs seem promising tools to facilitate immediate, intermediate, and long-term outcomes in older patients by providing information, enhancing information exchange, and promoting self-management. However, future studies should evaluate the effectiveness of OHITs for older patients to achieve stronger levels of evidence.


Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in western, northern, and eastern Cambodia, 2011-2012: association with molecular markers.
In 2008, dihydroartemisinin (DHA)-piperaquine (PPQ) became the first-line treatment for uncomplicated Plasmodium falciparum malaria in western Cambodia. Recent reports of increased treatment failure rates after DHA-PPQ therapy in this region suggest that parasite resistance to DHA, PPQ, or both is now adversely affecting treatment. While artemisinin (ART) resistance is established in western Cambodia, there is no evidence of PPQ resistance. To monitor for resistance to PPQ and other antimalarials, we measured drug susceptibilities for parasites collected in 2011 and 2012 from Pursat, Preah Vihear, and Ratanakiri, in western, northern, and eastern Cambodia, respectively. Using a SYBR green I fluorescence assay, we calculated the ex vivo 50% inhibitory concentrations (IC50s) of 310 parasites to six antimalarials: chloroquine (CQ), mefloquine (MQ), quinine (QN), PPQ, artesunate (ATS), and DHA. Geometric mean IC50s (GMIC50s) for all drugs (except PPQ) were significantly higher in Pursat and Preah Vihear than in Ratanakiri (P ≤ 0.001). An increased copy number of P. falciparum mdr1 (pfmdr1), an MQ resistance marker, was more prevalent in Pursat and Preah Vihear than in Ratanakiri and was associated with higher GMIC50s for MQ, QN, ATS, and DHA. An increased copy number of a chromosome 5 region (X5r), a candidate PPQ resistance marker, was detected in Pursat but was not associated with reduced susceptibility to PPQ. The ex vivo IC50 and pfmdr1 copy number are important tools in the surveillance of multidrug-resistant (MDR) parasites in Cambodia. While MDR P. falciparum is prevalent in western and northern Cambodia, there is no evidence for PPQ resistance, suggesting that DHA-PPQ treatment failures result mainly from ART resistance.


Hydrophobic Interactions between DNA Duplexes and Synthetic and Biological Membranes.
Equipping DNA with hydrophobic anchors enables targeted interaction with lipid bilayers for applications in biophysics, cell biology, and synthetic biology. Understanding DNA-membrane interactions is crucial for rationally designing functional DNA. Here we study the interactions of hydrophobically tagged DNA with synthetic and cell membranes using a combination of experiments and atomistic molecular dynamics (MD) simulations. The DNA duplexes are rendered hydrophobic by conjugation to a terminal cholesterol anchor or by chemical synthesis of a charge-neutralized alkyl-phosphorothioate (PPT) belt. Cholesterol-DNA tethers to lipid vesicles of different lipid compositions and charges, while PPT DNA binding strongly depends on alkyl length, belt position, and headgroup charge. Divalent cations in the buffer can also influence binding. Our MD simulations directly reveal the complex structure and energetics of PPT DNA within a lipid membrane, demonstrating that longer alkyl-PPT chains provide the most stable membrane anchoring but may disrupt DNA base paring in solution. When tested on cells, cholesterol-DNA is homogeneously distributed on the cell surface, while alkyl-PPT DNA accumulates in clustered structures on the plasma membrane. DNA tethered to the outside of the cell membrane is distinguished from DNA spanning the membrane by nuclease and sphingomyelinase digestion assays. The gained fundamental insight on DNA-bilayer interactions will guide the rational design of membrane-targeting nanostructures.


Lineage-specific combinatorial action of enhancers regulates mouse erythroid Gata1 expression.
Precise spatiotemporal control of Gata1 expression is required in both early hematopoietic progenitors to determine erythroid/megakaryocyte versus granulocyte/monocyte lineage output and in the subsequent differentiation of erythroid cells and megakaryocytes. An enhancer element upstream of the mouse Gata1 IE (1st exon erythroid) promoter, mHS-3.5, can direct both erythroid and megakaryocytic expression. However, loss of this element ablates only megakaryocytes, implying that an additional element has erythroid specificity. Here, we identify a double DNaseI hypersensitive site, mHS-25/6, as having erythroid but not megakaryocytic activity in primary cells. It binds an activating transcription factor complex in erythroid cells where it also makes physical contact with the Gata1 promoter. Deletion of mHS-25/6 or mHS-3.5 in embryonic stem cells has only a modest effect on in vitro erythroid differentiation, whereas loss of both elements ablates both primitive and definitive erythropoiesis with an almost complete loss of Gata1 expression. Surprisingly, Gata2 expression was also concomitantly low, suggesting a more complex interaction between these 2 factors than currently envisaged. Thus, whereas mHS-3.5 alone is sufficient for megakaryocytic development, mHS-3.5 and mHS-25/6 collectively regulate erythroid Gata1 expression, demonstrating lineage-specific differences in Gata1 cis-element use important for development of these 2 cell types.


Exclusion Through Inclusion. Struggles Over the Scalar Regimes of Belonging Europe and the Family at the 1995 Fourth UN World Conference on Women and the Agency of (Polish) Women.
Gender regimes of belonging are contextually variable and closely linked to other regimes of belonging, such as the family, the nation, or, the region. In the case of Poland, this contextuality and interdependence becomes apparent when analyzing struggles between feminist and Catholic anti-choice environments. While the first group opts for gender democracy, the other favors a familistic social order. In the mid-90s, the struggle over "Polish" gender regimes took an international dimension and was played out as well at the international fora of the UN. When women's rights actors from Poland appeared at the 4th World Conference on Women held by the UN in China in 1995, they experienced being positioned within a pre-structured spatial order and learned that this positioning and the synthesis within scalar regimes of belonging, such as the scale of family but also that of region, have a major impact on their political agency. The spatial order of the UN is a field of conflict, as certain positioning within regimes of belonging might limit political agency and therefore constrain the making of claims. NGOs struggle to get representation and definitional power over space and collective identity categories, but they also put effort into changing the very composition and hierarchies within identity regimes. Toward this end, they form coalitions and networks and perform group identities and may even act in opposition to institutionalized regimes of belonging. The use of concepts such as belonging and scale allows us to avoid the analytical limits that are linked to the theoretical frameworks of recognition and identity politics. This article explores the strategies of scalar politics of belonging applied by NGOs, which also lead to the establishment of bodies representing women from the post-socialist countries of Central and Eastern Europe, such as the Karat Coalition, but it also draws attention to the political effects of scaling belonging through the "family" or "Europe." Today, the question as to what shape gender regimes of belonging should take is still an important site of struggle.


Point-of-care lung ultrasound in COVID-19 patients: inter- and intra-observer agreement in a prospective observational study.
With an urgent need for bedside imaging of coronavirus disease 2019 (COVID-19), this study's main goal was to assess inter- and intraobserver agreement in lung ultrasound (LUS) of COVID-19 patients. In this single-center study we prospectively acquired and evaluated 100 recorded ten-second cine-loops in confirmed COVID-19 intensive care unit (ICU) patients. All loops were rated by ten observers with different subspeciality backgrounds for four times by each observer (400 loops overall) in a random sequence using a web-based rating tool. We analyzed inter- and intraobserver variability for specific pathologies and a semiquantitative LUS score. Interobserver agreement for both, identification of specific pathologies and assignment of LUS scores was fair to moderate (e.g., LUS score 1 Fleiss' κ = 0.27; subpleural consolidations Fleiss' κ = 0.59). Intraobserver agreement was mostly moderate to substantial with generally higher agreement for more distinct findings (e.g., lowest LUS score 0 vs. highest LUS score 3 (median Fleiss' κ = 0.71 vs. 0.79) or air bronchograms (median Fleiss' κ = 0.72)). Intraobserver consistency was relatively low for intermediate LUS scores (e.g. LUS Score 1 median Fleiss' κ = 0.52). We therefore conclude that more distinct LUS findings (e.g., air bronchograms, subpleural consolidations) may be more suitable for disease monitoring, especially with more than one investigator and that training material used for LUS in point-of-care ultrasound (POCUS) should pay refined attention to areas such as B-line quantification and differentiation of intermediate LUS scores.


An aerodynamic assisted miniature mass spectrometer for enhanced volatile sample analysis.
Previously, we have reported the development of a miniature mass spectrometer with a continuous atmospheric pressure interface (CAPI), and the use of it for non-volatile sample analysis, such as drugs, peptides and proteins. However due to the diffusion effects in the CAPI, especially stronger for light ions, the instrument shows low detection sensitivities for volatile samples when coupling with an atmosphere pressure chemical ionization (APCI) source (>ppmv). In this study, an in-vacuum plasma ionization source was designed and integrated into the system. By performing ionization in the first vacuum stage, ion transfer loss through the CAPI was minimized and tens of ppbv level detection sensitivities were achieved for volatile samples. Due to its improved sensitivity, chemical source tracing was demonstrated in an indoor environment as a simple proof-of-concept example. Furthermore, an aerodynamic sampling method was developed to facilitate directional sample transfer towards the miniature mass spectrometer in an open environment. By coupling this aerodynamic method with the miniature mass spectrometer, remote chemical source sensing could be achieved at a distance of more than two meters. This aerodynamic sampling method could also be applied to other mass spectrometry instruments for enhanced sample sampling in open environments.


Multiple methylation-free islands flank a small breakpoint cluster region on 11p13 in the t(11;14)(p13;q11) translocation.
The t(11;14)(p13;q11) translocation is one of the most frequent chromosomal abnormalities in T-cell acute lymphoblastic leukemia (ALL). Ten different leukemias carrying this translocation have been analysed and all 10 breakpoints fall within a region of less than 25 kb on chromosome band 11p13. We have used PFGE and cosmid cloning to assess the presence of potential genes by analysing methylation-free islands in the vicinity. Four methylation-free islands, within 270 kb, flank the t(11;14)-associated breakpoint cluster region (T-ALLbcr), one occurring about 25 kb on the telomeric side and one about 100 kb on the centromeric side of the T-ALLbcr. Evidence for eight further methylation-free islands on both sides of the T-ALLbcr region is also presented. Thus multiple methylation-free islands exist on 11p13 flanking the t(11;14)(p13;q11) translocation-associated breakpoint cluster region, representing multiple potential transcription units whose chromosomal environment is altered by chromosome translocation.


Racial differences in the accuracy of perceived partner HIV status among men who have sex with men (MSM) in Atlanta, Georgia.
We compared perceptions of partner HIV status to HIV test results in a cross-sectional study of sexual networks of men who have sex with men (MSM) in Atlanta. We then examined differences between black and white MSM in the predictive value of perceived partner status. We recruited men ("seeds") using time-space venue sampling. These seeds then referred up to three partners, who could also refer partners. All participants reported sexual behavior and HIV status for recent partners and received HIV tests. For partners who enrolled, we compared laboratory diagnoses to their partner's perception of their status. Black MSM who perceived themselves to be HIV negative were more likely than perceived-negative white MSM to have a positive partner among those they perceived to be HIV negative or whose status was unknown to them (OR=6.6). Furthermore, although frequency of unprotected anal intercourse (UAI) was similar by race, black men were more likely to have had UAI with an unknown-positive partner (OR=9.3).


Compound heterozygous CORO1A mutations in siblings with a mucocutaneous-immunodeficiency syndrome of epidermodysplasia verruciformis-HPV, molluscum contagiosum and granulomatous tuberculoid leprosy.
Coronin-1A deficiency is a recently recognized autosomal recessive primary immunodeficiency caused by mutations in CORO1A (OMIM 605000) that results in T-cell lymphopenia and is classified as T(-)B(+)NK(+)severe combined immunodeficiency (SCID). Only two other CORO1A-kindred are known to date, thus the defining characteristics are not well delineated. We identified a unique CORO1A-kindred. We captured a 10-year analysis of the immune-clinical phenotypes in two affected siblings from disease debut of age 7 years. Target-specific genetic studies were pursued but unrevealing. Telomere lengths were also assessed. Whole exome sequencing (WES) uncovered the molecular diagnosis and Western blot validated findings. We found the compound heterozygous CORO1A variants: c.248_249delCT (p.P83RfsX10) and a novel mutation c.1077delC (p.Q360RfsX44) (NM_007074.3) in two affected non-consanguineous siblings that manifested as absent CD4CD45RA(+) (naïve) T and memory B cells, low NK cells and abnormally increased double-negative (DN) ϒδ T-cells. Distinguishing characteristics were late clinical debut with an unusual mucocutaneous syndrome of epidermodysplasia verruciformis-human papilloma virus (EV-HPV), molluscum contagiosum and oral-cutaneous herpetic ulcers; the older female sibling also had a disfiguring granulomatous tuberculoid leprosy. Both had bilateral bronchiectasis and the female died of EBV+ lymphomas at age 16 years. The younger surviving male, without malignancy, had reproducibly very short telomere lengths, not before appreciated in CORO1A mutations. We reveal the third CORO1A-mutated kindred, with the immune phenotype of abnormal naïve CD4 and DN T-cells and newfound characteristics of a late/hypomorphic-like SCID of an EV-HPV mucocutaneous syndrome with also B and NK defects and shortened telomeres. Our findings contribute to the elucidation of the CORO1A-SCID-CID spectrum.


Effect of maxillomandibular fixation on condylar growth in juvenile Macaca mulatta: a cephalometric and histologic study.
The effect of maxillomandibular fixation on the growth of the mandibular condyle was studied in eight control and eight experimental male juvenile monkeys. All animals had metallic implants placed throughout the craniofacial complex in order to facilitate cephalometric analysis of growth-related changes in the maxillomandibular complex during jaw immobilization. Every 3, 6, 12, and 24 wk after insertion of the appliance two experimental animals were killed for histologic analysis. Cephalometric analysis indicated no major deviation from normal maxillary or mandibular growth in the experimental animals. The condylar growth in the experimental animals was comparable with that of the controls. Histologic analysis indicated that the articular connective tissue in experimental joints remained the same thickness as in the controls. On the postero-superior aspect of the condyle, the thickness of the prechondroblastic-chondroblastic cell layer was reduced by 70-80% in the experimental animals. On the posterior aspect this cell layer was not visible after 12 wk of fixation, but was replaced by a periosteum-like, cell-rich tissue which appeared to be active in appositional formation of cancellous bone. These results indicate that long-term maxillomandibular fixation does not cause major alterations in the growth of condyle or the entire mandible despite a profound decrease of the prechondroblastic-chondroblastic cell layer in the postero-superior and posterior regions of the condyle. The growth is probably due to a compensatory appositional bone formation along the surface of the condyle. It is also concluded that jaw mobility is not a prerequisite for normal maxillary or mandibular growth.


Hidden conditional random fields.
We present a discriminative latent variable model for classification problems in structured domains where inputs can be represented by a graph of local observations. A hidden-state Conditional Random Field framework learns a set of latent variables conditioned on local features. Observations need not be independent and may overlap in space and time.


Baseline bone mineral density and boneturnover in pre-operative hip and knee arthroplasty patients.
Osteoporosis and abnormal bone metabolism may prove to be significant factors influencing the outcome of arthroplasty surgery, predisposing to complications of aseptic loosening and peri-prosthetic fracture. We aimed to investigate baseline bone mineral density (BMD) and bone turnover in patients about to undergo arthroplasty of the hip and knee. We prospectively measured bone mineral density of the hip and lumbar spine using dual-energy X-ray absorptiometry (DEXA) scans in a cohort of 194 patients awaiting hip or knee arthroplasty. We also assessed bone turnover using urinary deoxypyridinoline (DPD), a type I collagen crosslink, normalised to creatinine. The prevalence of DEXA proven hip osteoporosis (T-score ≤ -2.5) among hip and knee arthroplasty patients was found to be low at 2.8% (4 of 143). Spinal osteoporosis prevalence was higher at 6.9% (12 of 175). Sixty patients (42% (60 of 143)) had osteopenia or osteoporosis of either the hip or spine. The mean T-score for the hip was -0.34 (sd 1.23), which is within normal limits, and the mean hip Z-score was positive at 0.87 (sd 1.17), signifying higher-than-average BMD for age. The median urinary DPD/creatinine was raised in both female patients at 8.1 (interquartile range (IQR) 6.6 to 9.9) and male patients at 6.2 (IQR 4.8 to 7.5). Our results indicate hip and knee arthroplasty patients have higher BMD of the hip and spine compared with an age-matched general population, and a lower prevalence of osteoporosis. However, untreated osteoporotic patients are undergoing arthroplasty, which may negatively impact their outcome. Raised DPD levels suggest abnormal bone turnover, requiring further investigation. Cite this article: Bone Joint Res 2014;3:14-19.


Pregnancy-associated plasma protein A as a marker of acute coronary syndromes.
Circulating markers indicating the instability of atherosclerotic plaques could have diagnostic value in unstable angina or acute myocardial infarction. We evaluated pregnancy-associated plasma protein A (PAPP-A), a potentially proatherosclerotic metalloproteinase, as a marker of acute coronary syndromes. We examined the level of expression of PAPP-A in eight culprit unstable coronary plaques and four stable plaques from eight patients who had died suddenly of cardiac causes. We also measured circulating levels of PAPP-A, C-reactive protein, and insulin-like growth factor I (IGF-I) in 17 patients with acute myocardial infarction, 20 with unstable angina, 19 with stable angina, and 13 controls without atherosclerosis. PAPP-A was abundantly expressed in plaque cells and extracellular matrix of ruptured and eroded unstable plaques, but not in stable plaques. Circulating PAPP-A levels were significantly higher in patients with unstable angina or acute myocardial infarction than in patients with stable angina and controls (P<0.001). A PAPP-A threshold value of 10 mlU per liter identified patients who had acute coronary syndromes with a sensitivity of 89.2 percent and a specificity of 81.3 percent. PAPP-A levels correlated with levels of C-reactive protein and free IGF-I, but not with markers of myocardial injury (troponin I and the MB isoform of creatine kinase). PAPP-A is present in unstable plaques, and circulating levels are elevated in acute coronary syndromes; these increased levels may reflect the instability of atherosclerotic plaques. PAPP-A is a new candidate marker of unstable angina and acute myocardial infarction.


Zoos and public health: A partnership on the One Health frontier.
Today, accredited zoos are not just places for entertainment, they are actively involved in research for conservation and health. During recent decades in which the challenges for biodiversity conservation and public health have escalated, zoos have made significant changes to address these difficulties. Zoos increasingly have four key areas of focus: education, recreation, conservation, and research. These key areas are important in addressing an interrelated global conservation (i.e. habitat and wildlife loss) and public health crisis. Zoo and public health professionals working together within a One Health framework represent a powerful alliance to address current and future conservation and public health problems around the world. For researchers, practitioners, and students, the collaboration between zoos and public health institutions offers the opportunity to both teach and operationalize this transdisciplinary approach. Using examples from our programs, we give a template for moving forward with collaborative initiatives and sustainable solutions involving partners in both zoos and public health institutions. We provide examples of cooperative programs and suggest a model for consideration in the development of further activities in this area.


Cortical regions involved in the generation of musical structures during improvisation in pianists.
Studies on simple pseudorandom motor and cognitive tasks have shown that the dorsolateral prefrontal cortex and rostral premotor areas are involved in free response selection. We used functional magnetic resonance imaging to investigate whether these brain regions are also involved in free generation of responses in a more complex creative behavior: musical improvisation. Eleven professional pianists participated in the study. In one condition, Improvise, the pianist improvised on the basis of a visually displayed melody. In the control condition, Reproduce, the participant reproduced his previous improvisation from memory. Participants were able to reproduce their improvisations with a high level of accuracy, and the contrast Improvise versus Reproduce was thus essentially matched in terms of motor output and sensory feedback. However, the Improvise condition required storage in memory of the improvisation. We therefore also included a condition FreeImp, where the pianist improvised but was instructed not to memorize his performance. To locate brain regions involved in musical creation, we investigated the activations in the Improvise-Reproduce contrast that were also present in FreeImp contrasted with a baseline rest condition. Activated brain regions included the right dorsolateral prefrontal cortex, the presupplementary motor area, the rostral portion of the dorsal premotor cortex, and the left posterior part of the superior temporal gyrus. We suggest that these regions are part of a network involved in musical creation, and discuss their possible functional roles.


First Report of Enterobacter cowanii Causing Bacterial Spot on Mabea fistulifera, a Native Forest Species in Brazil.
In the summer of 2011, in a nursery located in Viçosa City, Minas Gerais State, brownish, necrotic, irregular spots were observed on leaves of Mabea fistulifera Mart. (Euphorbiaceae), an indigenous forest species commonly found in Brazil. Around 6,300 seedlings were evaluated and as many as 60% of them showed disease symptoms, including severe defoliation and plant death. Leaves with coalescing lesions turned papery in texture and had a blighted appearance. Bacterial colonies were isolated from these symptomatic leaves on King B's medium and identified based on biochemical and molecular analysis, as a member of the Enterobacteriaceae family. Like other members of the Enterobacteriaceae family, the bacteria were facultative anaerobic, gram-negative, cream-colored on YDC medium, urease and oxidase negative, as well as catalase and asparagine positive. Bacterial DNA was extracted from pure culture grown overnight in liquid 523 medium at 28°C using the Wizard Genomic DNA Purification kit (Promega) and conserved sequences in 16S rDNA (3) and rpoB (1) were amplified by PCR. The sequence of the 1,300-bp 16S rDNA fragment and the 750-bp rpoB gene were analyzed by NCBI BLAST. Related sequences were aligned and analyzed by ClustalW in MEGA 5 software. Phylogenetic analysis by maximum likelihood, using PAUP version 4.0 and TBR algorithm with 1,000 bootstrap replications, grouped the isolate in a clade with Enterobacter cowanii and the result showed 99% and 98% identity to the 16s rDNA and rpoB, respectively. The isolate clustered closely with the type strain of E. cowanii in both phylogenetic trees constructed. Pathogenicity tests were carried out by inoculating leaves of healthy seedlings either by spraying or cutting with a scissor previously dipped into a 108 CFU/ml bacterial suspension. The experiment was in a completely randomized design, with six replications. A pot with one plant was considered one experimental unit. Control seedlings were sprayed or cut with a scissor treated with saline solution. Prior to and after inoculation, plants were kept in a humid chamber for 24 h at 26°C in the dark and at room temperature. Subsequently, plants were transferred to growth chamber at 26°C, under a 12-h photoperiod (40 μmol/s/m2). Consistent with the symptoms observed originally, 7 days after inoculation, all seedlings developed leaf spots. No characteristic symptoms could be observed in the negative control. Furthermore, Koch's postulates were confirmed by reisolation of the bacterium from symptomatic tissues. In summary, the phenotypic, biochemical, and molecular tests identified the pathogen as E. cowanii. Recently, E. cowanii was isolated from Eucalyptus trees with symptoms of bacterial blight, although its pathogenicity was not demonstrated (2). To the best of our knowledge, this is the first report of a member of the Enterobacteriaceae family causing disease in M. fistulifera. The result has a great importance to better understand the role of E. cowanii as a pathogen-causing disease on a forest species. References: (1) C. L. Brady et al. Syst. Appl. Microbiol. 31:447, 2008. (2) C. L. Brady et al. Lett. Appl. Microbiol. 49:461, 2009. (3) W. G. Weisburg et al. J. Bacteriol. 173:697, 1991.


Bounded empathy: neural responses to outgroup targets' (mis)fortunes.
The current study investigates whether mere stereotypes are sufficient to modulate empathic responses to other people's (mis)fortunes, how these modulations manifest in the brain, and whether affective and neural responses relate to endorsing harm against different outgroup targets. Participants feel least bad when misfortunes befall envied targets and worst when misfortunes befall pitied targets, as compared with ingroup targets. Participants are also least willing to endorse harming pitied targets, despite pitied targets being outgroup members. However, those participants who exhibit increased activation in functionally defined insula/middle frontal gyrus when viewing pity targets experience positive events not only report feeling worse about those events but also more willing to harm pity targets in a tradeoff scenario. Similarly, increased activation in anatomically defined bilateral anterior insula, in response to positive events, predicts increased willingness to harm envy targets, but decreased willingness to harm ingroup targets, above and beyond self-reported affect in response to the events. Stereotypes' specific content and not just outgroup membership modulates empathic responses and related behavioral consequences including harm.


Use of near infrared femtosecond lasers as sub-micron radiation microbeam for cell DNA damage and repair studies.
Laser induced radiation microbeam technology for radiobiology research is undergoing rapid growth because of the increased availability and ease of use of femtosecond laser sources. The main processes involved are multiphoton absorption and/or plasma formation. The high peak powers these lasers generate make them ideal tools for depositing sub-micrometer size radiant energy within a region of a living cell nucleus to activate ionising and/or photochemically driven processes. The technique allows questions relating to the effects of low doses of radiation, the propagation and treatment of deoxyribonucleic acid (DNA) damage and repair in individual live cells as well as non-targeted cell to cell effects to be addressed. This mini-review focuses on the use of near infrared (NIR) ca. 800nm radiation to induce damage that is radically different from the early and subsequent ultraviolet microbeam techniques. Ultrafast pulsed NIR instrumentation has many benefits including the ability to eliminate issues of unspecific UV absorption by the many materials prevalent within cells. The multiphoton interaction volume also permits energy deposition beyond the diffraction limit. Work has established that the fundamental process of the damage induced by the ultrashort laser pulses is different to those induced from continuous wave light sources. Pioneering work has demonstrated that NIR laser microbeam radiation can mimic ionising radiation via multiphoton absorption within the 3D femtolitre volume of the highly focused Gaussian beam. This light-matter interaction phenomenon provides a novel optical microbeam probe for mimicking both complex ionising and UV radiation-type cell damage including double strand breaks (DSBs) and base damage. A further advantage of the pulsed laser technique is that it provides further scope for time-resolved experiments. Recently the NIR laser microbeam technique has been used to investigate the recruitment of repair proteins to the sub-micrometre size area of damage in viable cells using both immuno-fluorescent staining of gamma-H2AX (a marker for DSBs) and real-time imaging of GFP-labelled repair proteins including ATM, p53 binding protein 1 (53BP1), RAD51 and Ku 70/80 to elucidate the interaction of the two DNA DSB repair pathways, homologous recombination and the non-homologous end joining pathway.


B-mode real time ultrasonographic imaging of the testis and epididymis of sheep and goats.
Ten male goats and five rams were examined from 11 and 15 weeks of age, respectively, for six months to study the ultrasonic appearance of normal testes and epididymides before and after puberty. Five adult rams with lesions of these organs were also examined. A portable, B-mode, real time scanner fitted with a 7.5 MHz, linear array transducer was used. The testis appeared as a homogeneous and moderately echogenic structure with a centrally located mediastinum testis represented by an hyperechogenic line in images taken in the longitudinal plane and by an almost circular spot in transverse images. The testicular capsule and skin were evident as a distinct hyperechogenic line encircling the testicular parenchyma. A thin non-echogenic layer of fluid, presumably between two layers of tunica vaginalis, was observed. The tail of the epididymis was more heterogeneous and less echogenic than the testis. The epididymal head was also less echogenic but homogeneous in texture, and the body of the epididymis was difficult to image. The pampiniform plexus was easily identified as numerous convoluted sonolucent tubular structures. The ultrasonic images of possible cases of epididymitis, spermatocele, testicular cyst and abscess and scrotal hernia are described.


A prototype high-speed optically-steered X-band phased array antenna.
We develop a prototype of optically-steered X-band phased array antenna with capabilities of multi-band and multi-beam operations. It exploits high-speed wavelength tunable lasers for optical true-time delays over a dispersive optical fiber link, enabling agile, broadband and vibration-free RF beam steering with large angle.


Defining the hypoxic target volume based on positron emission tomography for image guided radiotherapy - the influence of the choice of the reference region and conversion function.
Hypoxia imaged by positron emission tomography (PET) is a potential target for optimization in radiotherapy. However, the implementation of this approach with respect to the conversion of intensities in the images into oxygenation and radiosensitivity maps is not straightforward. This study investigated the feasibility of applying two conversion approaches previously derived for 18F-labeled fluoromisonidazole (18F-FMISO)-PET images for the hypoxia tracer 18F-flortanidazole (18F-HX4). Ten non-small-cell lung cancer patients imaged with 18F-HX4 before the start of radiotherapy were considered in this study. PET image uptake was normalized to a well-oxygenated reference region and subsequently linear and non-linear conversions were used to determine tissue oxygenations maps. These were subsequently used to delineate hypoxic volumes based partial oxygen pressure (pO2) thresholds. The results were compared to hypoxic volumes segmented using a tissue-to-background ratio of 1.4 for 18F-HX4 uptake. While the linear conversion function was not found to result in realistic oxygenation maps, the non-linear function resulted in reasonably sized sub-volumes in good agreement with uptake-based segmented volumes for a limited range of pO2 thresholds. However, the pO2 values corresponding to this range were significantly higher than what is normally considered as hypoxia. The similarity in size, shape, and relative location between uptake-based sub-volumes and volumes based on the conversion to pO2 suggests that the relationship between uptake and pO2 is similar for 18F-FMISO and 18F-HX4, but that the model parameters need to be adjusted for the latter. A non-linear conversion function between uptake and oxygen partial pressure for 18F-FMISO-PET could be applied to 18F-HX4 images to delineate hypoxic sub-volumes of similar size, shape, and relative location as based directly on the uptake. In order to apply the model for e.g., dose-painting, new parameters need to be derived for the accurate calculation of dose-modifying factors for this tracer.


The Changing Landscape of Legume Products Available in Australian Supermarkets.
Evidence supports regular dietary inclusion of legumes due to their positive effects on both human and planetary health. Intake within Australia is suboptimal, with consumer data suggesting that an inability to integrate legumes into usual dietary patterns is a barrier to consumption. This places the food industry in a unique position to offer Australians the ability to incorporate legumes into usual dietary patterns via innovative new products. The aim of this study was to explore the legume category and compare nutrition product data and the use of nutrition and health claims between 2019 and 2021. An audit of legume products from four major metropolitan Sydney supermarkets (Aldi, Coles, IGA, Woolworths) collected ingredient lists, nutrition information and on-pack claims for baked beans, legume dips, legume flours, legume snacks (including subcategories of legume chips and whole legume snacks), canned legumes, dried legumes, frozen legumes, and pulse pasta. The total number of legume products available on the market nearly doubled from 2019 (n = 312) to 2021 (n = 610); this was driven by traditional plain canned and dried legumes and some new and convenient options, particularly snacks (legume chips) where the largest growth occurred. Of all legume products (n = 610), 82% met the Nutrient Profiling Scoring Criteria, 86.8% were at least a source of dietary fibre, and 55.9% were at least a source of protein. Nutrition content claims relating to dietary fibre, gluten free and protein more than doubled since 2019, with each featuring on over one third of the products identified in 2021. Vegan/vegetarian on-pack claims more than doubled since 2019, and claims related to the term plant-based/plant protein and environmental sustainability emerged on packs in 2021. By addressing barriers to consumption, such as lack of time and knowledge on how to prepare legumes, innovative legume products may help influence future consumption patterns.


Diagnostic utility of direct immunofluorescence findings around hair follicles and sweat glands in immunobullous disease.
Inherent to some immunobullous disorders is potential for intraepidermal or dermal-epidermal junction fragility, a phenomenon that may compromise biopsy specimen integrity and direct immunofluorescence (DIF) interpretation. In these situations, cutaneous adnexal structures (e.g. hair follicles, sweat apparatus) usually remain intact. Whether periadnexal DIF findings are reliable in diagnosing immunobullous conditions is unknown. We evaluated 56 cutaneous specimens with diagnostic immunoglobulin (Ig) deposition patterns that contained adnexal structures. In a corollary study, we examined 145 hematoxylin-eosin-stained frozen specimens to determine biopsy factors associated with the presence of adnexal structures. Periadnexal DIF findings offered diagnostic sensitivity in conditions with linear or cell-surface Ig deposition or lupus band. Periadnexal DIF findings were unreliable in dermatitis herpetiformis. Biopsy specimens from scalp and genitalia were most likely to contain folliculosebaceous units and sweat duct apparatus, respectively. Relative depth of biopsy correlated directly with the likelihood of identifying sweat duct apparatus but not folliculosebaceous units. Periadnexal DIF findings may add diagnostic sensitivity in DIF evaluation of pemphigoid, pemphigus and lupus erythematosus. Pathologists can guide clinicians to biopsy certain anatomic sites and to obtain sufficient biopsy depth to increase the probability of capturing adnexal structures and, therefore, diagnostic yield from DIF specimens.


Preparation of magnetic dummy molecularly imprinted polymers for selective extraction and analysis of salicylic acid in Actinidia chinensis.
Compounds with strong intramolecular hydrogen bonds (e.g., salicylic acid) have weak intermolecular hydrogen bonding interactions between them and functional monomers in the imprinting process. Consequently, the corresponding molecularly imprinted polymers (MIPs) have no specific adsorption ability. Here, the first magnetic dummy MIPs (MDMIPs) based on benzonic acid as dummy template are successfully developed and evaluated with respect to the applications in selective enrichment and analysis of salicylic acid from complex mixtures. Various parameters affecting absorption/desorption were evaluated for achieving optimal recovery and reducing nonspecific interactions. The prepared MDMIPs showed high adsorption capacity, good selectivity, rapid kinetic binding (40 min) and magnetic separation (5 s), high reproducibility (RSD< 4 % for batch-to-batch evaluation), and stability (only 4 % decrease after 6 cycles). Owing to the efficacy in specific binding and removal of interference, trace level salicylic acid was quantified (0.2 μg/g of fresh mass) in Actinidia chinensis by high-performance liquid chromatography.


European multicenter study on antimicrobial resistance in bacteria isolated from companion animal urinary tract infections.
There is a growing concern regarding the increase of antimicrobial resistant bacteria in companion animals. Yet, there are no studies comparing the resistance levels of these organisms in European countries. The aim of this study was to investigate geographical and temporal trends of antimicrobial resistant bacteria causing urinary tract infection (UTI) in companion animals in Europe. The antimicrobial susceptibility of 22 256 bacteria isolated from dogs and cats with UTI was determined. Samples were collected between 2008 and 2013 from 16 laboratories of 14 European countries. The prevalence of antimicrobial resistance of the most common bacteria was determined for each country individually in the years 2012-2013 and temporal trends of bacteria resistance were established by logistic regression. The aetiology of uropathogenic bacteria differed between dogs and cats. For all bacterial species, Southern countries generally presented higher levels of antimicrobial resistance compared to Northern countries. Multidrug-resistant Escherichia coli were found to be more prevalent in Southern countries. During the study period, the level of fluoroquinolone-resistant E. coli isolated in Belgium, Denmark, France and the Netherlands decreased significantly. A temporal increase in resistance to amoxicillin-clavulanate and gentamicin was observed among E. coli isolates from the Netherlands and Switzerland, respectively. Other country-specific temporal increases were observed for fluoroquinolone-resistant Proteus spp. isolated from companion animals from Belgium. This work brings new insights into the current status of antimicrobial resistance in bacteria isolated from companion animals with UTI in Europe and reinforces the need for strategies aiming to reduce resistance.


Environment perception and leisure-time physical activity in Portuguese high school students.
This study aims to analyze the association between perceived environmental factors and leisure-time physical activity (PA) among adolescents of both genders. Data were collected in autumn of 2011 from 866 adolescents (412 girls and 454 boys) 12- to 18-years-old, from four Portuguese cities. Perception of environmental factors was assessed by Assessing Levels of Physical Activity and Fitness (ALPHA) questionnaire (Spittaels et al., 2010, IJBNPA). PA was assessed by a questionnaire that evaluated PA during leisure-time and participants were assigned into the following categories: sedentary; low active; moderate active; and very active. Boys presented higher levels of structured PA, frequency and intensity of PA, and level of sport competition than girls (p < 0.001). Distance to local facilities (p = 0.001 for girls; p < 0.001 for boys) and home environment (p = 0.004 for girls; p = 0.015 for boys) were negatively associated with PA. Total, cycling and walking infrastructures (p < 0.001), as well as cycling and walking network (p = 0.049) and connectivity (p = 0.034) showed a positive association with PA in boys. Analysis of variance showed significant differences between girls' PA regarding aesthetics (p = 0.013), study environment (p = 0.023), home environment (p = 0.014) and whether it is pleasant or not (p = 0.023). Differences between boys' PA were observed for distance to local facilities (p = 0.003), total, cycling and walking infrastructures (p < 0.001) and home environment (p = 0.002). This study results support that some environmental factors are associated with adolescents' PA levels, with relevant differences between genders. Therefore, these gender differences must be taken into account, in order to increase levels of PA in Portuguese youth, especially in girls.


Transcriptome analysis revealed the dynamic oil accumulation in Symplocos paniculata fruit.
Symplocos paniculata, asiatic sweetleaf or sapphire berry, is a widespread shrub or small tree from Symplocaceae with high oil content and excellent fatty acid composition in fruit. It has been used as feedstocks for biodiesel and cooking oil production in China. Little transcriptome information is available on the regulatory molecular mechanism of oil accumulation at different fruit development stages. The transcriptome at four different stages of fruit development (10, 80,140, and 170 days after flowering) of S. paniculata were analyzed. Approximately 28 million high quality clean reads were generated. These reads were trimmed and assembled into 182,904 non-redundant putative transcripts with a mean length of 592.91 bp and N50 length of 785 bp, respectively. Based on the functional annotation through Basic Local Alignment Search Tool (BLAST) with public protein database, the key enzymes involved in lipid metabolism were identified, and a schematic diagram of the pathway and temporal expression patterns of lipid metabolism was established. About 13,939 differentially expressed unigenes (DEGs) were screened out using differentially expressed sequencing (DESeq) method. The transcriptional regulatory patterns of the identified enzymes were highly related to the dynamic oil accumulation along with the fruit development of S. paniculata. In addition, quantitative real-time PCR (qRT-PCR) of six vital genes was significantly correlated with DESeq data. The transcriptome sequences obtained and deposited in NCBI would enrich the public database and provide an unprecedented resource for the discovery of the genes associated with lipid metabolism pathway in S. paniculata. Results in this study will lay the foundation for exploring transcriptional regulatory profiles, elucidating molecular regulatory mechanisms, and accelerating genetic engineering process to improve the yield and quality of seed oil of S. paniculata.


DNA unwinding is an Mcm complex-dependent and ATP hydrolysis-dependent process.
Minichromosome maintenance proteins (Mcm) are essential in all eukaryotes and are absolutely required for initiation of DNA replication. The eukaryotic and archaeal Mcm proteins have conserved helicase motifs and exhibit DNA helicase and ATP hydrolysis activities in vitro. Although the Mcm proteins have been proposed to be the replicative helicase, the enzyme that melts the DNA helix at the replication fork, their function during cellular DNA replication elongation is still unclear. Using nucleoplasmic extract (NPE) from Xenopus laevis eggs and six purified polyclonal antibodies generated against each of the Xenopus Mcm proteins, we have demonstrated that Mcm proteins are required during DNA replication and DNA unwinding after initiation of replication. Quantitative depletion of Mcms from the NPE results in normal replication and unwinding, confirming that Mcms are required before pre-replicative complex assembly and dispensable thereafter. Replication and unwinding are inhibited when pooled neutralizing antibodies against the six different Mcm2-7 proteins are added during NPE incubation. Furthermore, replication is blocked by the addition of the Mcm antibodies after an initial period of replication in the NPE, visualized by a pulse of radiolabeled nucleotide at the same time as antibody addition. Addition of the cyclin-dependent kinase 2 inhibitor p21(cip1) specifically blocks origin firing but does not prevent helicase action. When p21(cip1) is added, followed by the non-hydrolyzable analog ATPgammaS to block helicase function, unwinding is inhibited, demonstrating that plasmid unwinding is specifically attributable to an ATP hydrolysis-dependent function. These data support the hypothesis that the Mcm protein complex functions as the replicative helicase.


Blue-coloured highly efficient dye-sensitized solar cells by implementing the diketopyrrolopyrrole chromophore.
The paradigm shift in dye sensitized solar cells (DSCs) - towards donor- π bridge-acceptor (D-π-A) dyes - increases the performances of DSCs and challenges established design principles. Framed by this shifting landscape, a series of four diketopyrrolopyrrole (DPP)-based sensitizers utilizing the donor-chromophore-anchor (D-C-A) motif were investigated computationally, spectroscopically, and fabricated by systematic evaluation of finished photovoltaic cells. In all cases, the [Co(bpy)3](3+/2+) redox-shuttle afforded superior performance compared to I3(-)/I(-). Aesthetically, careful molecular engineering of the DPP chromophore yielded the first example of a high-performance blue DSC - a challenge unmet since the inception of this photovoltaic technology: DPP17 yields over 10% power conversion efficiency (PCE) with the [Co(bpy)3](3+/2+) electrolyte at full AM 1.5 G simulated sun light.


Renal Vasoconstriction Occurs Early During Shockwave Lithotripsy in Humans.
In animal models, pretreatment with low-energy shock waves and a pause decreased renal injury from shockwave lithotripsy (SWL). This is associated with an increase in perioperative renal resistive index (RI). A perioperative rise is not seen without the protective protocol, which suggests that renal vasoconstriction during SWL plays a role in protecting the kidney from injury. The purpose of our study was to investigate whether there is an increase in renal RI during SWL in humans. Subjects were prospectively recruited from two hospitals. All subjects received an initial 250 shocks at low setting, followed by a 2-minute pause. Treatment power was then increased. Measurements of the renal RI were taken before start of procedure, at 250, after 750, after 1500 shocks, and at the end of the procedure. A linear mixed-effects model was used to compare RIs at the different time points. Fifteen patients were enrolled. Average treatment time was 46 ± 8 minutes. Average RI at pretreatment, after 250, after 750, after 1500 shocks, and post-treatment was 0.67 ± 0.06, 0.69 ± 0.08, 0.71 ± 0.07, 0.73 ± 0.07, and 0.74 ± 0.06, respectively. In adjusted analyses, RI was significantly increased after 750 shocks compared with pretreatment (p = 0.05). Renal RI increases early during SWL in humans with the protective protocol. Monitoring for a rise in RI during SWL is feasible and may provide real-time feedback as to when the kidney is protected.


Hepatoprotective Effects of Grape Seed Procyanidin B2 in Rats With Carbon Tetrachloride-induced Hepatic Fibrosis.
Infectious hepatitis is a serious problem affecting millions of people worldwide, particularly in China and other developing countries, and it is the major risk factor for hepatic cirrhosis. To date, the pathogenesis of hepatic cirrhosis is complex and unclear. Traditional Chinese medicine (TCM) has long been used in its treatment; however, little is known to date about the effects of grape seed procyanidin B2 (GSPB2) on liver fibrosis. Using a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis, the study intended to investigate the hepatoprotective effects of GSPB2 and to determine the possible pathway by which GSPB2 exerts its activities. Design • Thirty-six male, Sprague-Dawley rats were used in the study. Rats in a model (CCl4 only) group and the GSPB2 group were given CCl4 to induce hepatic fibrosis. Simultaneously, animals in the GSPB2 group were treated with GSPB2 by intragastric administration for 12 wk. In addition, the rat's Kupffer cells were cultured with CCl4 and GSPB2. The study took place at the central laboratory of Qilu Hospital at Shandong University in Jinan, China. The following parameters were investigated: (1) hepatic function; (2) the liver fibrosis index-serum hyaluronic acid (HA), laminin (LN), type 3 procollagen (PC-3), collagen 4, and hepatic hydroxyproline; (3) the expression in the liver of transforming growth factor β-1 (TGF-β1); (4) inflammatory cytokines in the liver and cell culture medium-tumor necrosis factor α (TNF-α), interleukin (IL) 1-β (IL-1β), IL-6, and IL-17; (5) oxidative stress markers in the liver and cell culture medium-malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC); and (6) levels of angiotensin 2 (Ang 2) in the liver. The CCl4 induced (1) significant hepatic-function damage; (2) elevated levels of the measures of the liver fibrosis index, TGF-β1, inflammatory cytokines, MDA, and 8-OHdG; (3) a reduction in the activities of T-SOD and T-AOC; and (4) no effect on the level of expression of hepatic Ang 2. GSPB2 treatment partially reversed the changes induced by CCl4. The cell culture also showed that CCl4 elevated the levels of inflammatory cytokines and MDA in the Kupffer cell culture medium, whereas it reduced the activities of T-SOD and T-AOC in the medium. GSPB2 treatment partially reversed the changes induced by CCl4. GSPB2 had hepatoprotective effects on CCl4-induced hepatic fibrosis in Sprague-Dawley rats and inhibited the inflammatory response and oxidative stress in vivo and in vitro.


Coffee and tea consumption in relation to prostate cancer prognosis.
Bioactive compounds found in coffee and tea may delay the progression of prostate cancer. We investigated associations of pre-diagnostic coffee and tea consumption with risk of prostate cancer recurrence/progression. Study participants were men diagnosed with prostate cancer in 2002-2005 in King County, Washington, USA. We assessed the usual pattern of coffee and tea consumption two years before diagnosis date. Prostate cancer-specific outcome events were identified using a detailed follow-up survey. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). The analysis of coffee intake in relation to prostate cancer recurrence/progression included 630 patients with a median follow-up of 6.4 years, during which 140 prostate cancer recurrence/progression events were recorded. Approximately 61 % of patients consumed at least one cup of coffee per day. Coffee consumption was associated with a reduced risk of prostate cancer recurrence/progression; the adjusted HR for ≥4 cups/day versus ≤1 cup/week was 0.41 (95 % CI: 0.20, 0.81; p for trend = 0.01). Approximately 14 % of patients consumed one or more cups of tea per day, and tea consumption was unrelated to prostate cancer recurrence/progression. Results indicate that higher pre-diagnostic coffee consumption is associated with a lower risk of prostate cancer recurrence/progression. This finding will require replication in larger studies.


A facile route to prepare functional mesoporous organosilica spheres with electroactive units for chiral recognition of amino acids.
Conductive materials are valuable supports and widely applied in electrochemical analysis. In the current article, a mesoporous organosilica sphere (S,S)-CPMO-3 with the chiral group and electroactive units is presented. The organosilicon framework is composed of free ions belonging to the ionic liquid and the chiral group arising from (1S,2S)-1,2-diaminocyclohexane. Next, a bare electrode was modified by the as-synthesized composite material to construct the new electrochemical sensor (S,S)-CPMO-3-GCE. It was observed that (S,S)-CPMO-3-GCE exhibited favourable enantioselective recognition in the response of the peak current (Ip) and the peak potential (Ep) to the different configurations of amino acids. Taking tryptophan as an example, the value of IL/ID is 13.84 and the peak-to-peak potential approaches 48 mV. In addition, cysteine and tyrosine were successfully distinguished by the sensor. In summary, this study not only introduces a route for the synthesis of a conductive material, but also opens up its further potential in enantioselective recognition.


Lauroside B, a megastigmane glycoside from Laurus nobilis (bay laurel) leaves, induces apoptosis in human melanoma cell lines by inhibiting NF-κB activation.
Malignant melanoma is a highly aggressive tumor that frequently resists chemotherapy, so the search for new agents for its treatment is of great importance. In the present study, the antiproliferative propensity against human melanoma cell lines of lauroside B (1), a megastigmane glycoside isolated from Laurus nobilis (bay laurel) leaves, was investigated. This compound suppressed the proliferation of three human melanoma cell lines, namely, A375, WM115, and SK-Mel-28. The 1-induced inhibition of human melanoma cell proliferation was due to the induction of apoptosis, as demonstrated by FACS analysis with annexin V/PI staining and confirmed by activation of caspase-3 and by the cleavage of poly(ADP-ribose) polymerase (PARP). Growing evidence implicates NF-κB as an important contributor to metastasis and increased chemoresistance of melanoma. Thus, it was hypothesized that 1-induced apoptosis could be associated with suppression of NF-κB activation. The results showed that exposure of human melanoma cells to 1 inhibited IκB-α degradation and constitutive NF-κB DNA-binding activity as well as the expression, regulated by NF-κB, of two antiapoptotic genes, XIAP and c-FLIP. Induction of apoptosis by 1 in human aggressive melanoma cell lines has a potential high biological value.


Compendium of Animal Rabies Prevention and Control, 2007: National Association of State Public Health Veterinarians, Inc. (NASPHV).
Rabies is a fatal viral zoonosis and a serious public health problem. The disease is an acute progressive encephalitis caused by a lyssavirus. Multiple viral variants are maintained in wild mammal populations in the United States, but all mammals are believed to be susceptible to the disease. For purposes of this document, use of the term "animal" refers to mammals. The recommendations in this compendium serve as a basis for animal rabies-prevention and -control programs throughout the United States and facilitate standardization of procedures among jurisdictions, thereby contributing to an effective national rabies-control program. This document is reviewed annually and revised as necessary. These recommendations do not supersede state and local laws or requirements. Principles of rabies prevention and control are detailed in Part I; recommendations for parenteral vaccination procedures are presented in Part II, and all animal rabies vaccines licensed by the U.S. Department of Agriculture (USDA) and marketed in the United States are listed in Part III.


Multicystic mesothelioma: Operative and long-term outcomes with cytoreductive surgery and hyperthermic intra peritoneal chemotherapy.
Multicystic peritoneal mesothelioma (MCPM) is an extremely rare disease with 40-50% rate of recurrence after surgical debulking. Due to the recurrent nature of the disease, the option of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was offered for this condition. In the present study we aimed to describe the outcomes of this strategy in a single center cohort. We retrospectively reviewed a prospectively collected database of all patients with MCPM that underwent the combined procedure in our center. Clinical presentation, operative procedures and outcomes were reviewed. Between August 1997 and October 2017, 19 patients with MCPM underwent 20 cytoreduction and HIPEC procedures in our center. The majority of the patients were females (n = 17, 89%), and mean age was 42, as reported in other series. Disease extent, as measured by mean peritoneal carcinomatosis index (PCI) was 15.5 ± 9.9 and total number of procedures performed 6.7 ± 2.6. Major complications occurred in 3 (15%) patients, with no perioperative mortality. After a median of follow-up of 69 months (range 4-220) all patients were alive and 4 patients had recurrence (21%). Patients with high PCI (defined by median PCI) had shorter recurrence free survival (RFS) than patient with low PCI (mean RFS = 106.4 ± 6.6 for high PCI vs. 125.6 ± 34.1 for low PCI, p = 0.03). Cytoreduction and HIPEC offer low recurrence rate and prolonged mean RFS for patients with MCPM. The combined procedure can be offered with acceptable morbidity in specialized centers.


Coordination of care by primary care practices: strategies, lessons and implications.
Despite calls from numerous organizations and payers to improve coordination of care, there are few published accounts of how care is coordinated in real-world primary care practices. This study by the Center for Studying Health System Change (HSC) documents strategies that a range of physician practices use to coordinate care for their patients. While there was no single recipe for coordination given the variety of patient, physician, practice and market factors, some cross-cutting lessons were identified, such as the value of a commitment to interpersonal continuity of care as a foundation for coordination. Respondents also identified the importance of system support for the standardization of office processes to foster care coordination. While larger practices may have more resources to invest, many of the innovations described could be scaled to smaller practices. Some coordination strategies resulted in improved efficiency over time for practices, but by and large, physician practices currently pursue these efforts at their own expense. In addition to sharing information on effective strategies among practices, the findings also provide policy makers with a snapshot of the current care coordination landscape and implications for initiatives to improve coordination. Efforts to provide technical support to practices to improve coordination, for example, through medical-home initiatives, need to consider the baseline more typical practices may be starting from and tailor their support to practices ranging widely in size, resources and presence of standardized care processes. If aligned with payment incentives, some of these strategies have the potential to increase quality and satisfaction among patients and providers by helping to move the health care delivery system toward better coordinated care.


Interplay of inhibition and excitation shapes a premotor neural sequence.
In the zebra finch, singing behavior is driven by a sequence of bursts within premotor neurons located in the forebrain nucleus HVC (proper name). In addition to these excitatory projection neurons, HVC also contains inhibitory interneurons with a role in premotor patterning that is unclear. Here, we used a range of electrophysiological and behavioral observations to test previously described models suggesting discrete functional roles for inhibitory interneurons in song production. We show that single HVC premotor neuron bursts are sufficient to drive structured activity within the interneuron network because of pervasive and facilitating synaptic connections. We characterize interneuron activity during singing and describe reliable pauses in the firing of those neurons. We then demonstrate that these gaps in inhibition are likely to be necessary for driving normal bursting behavior in HVC premotor neurons and suggest that structured inhibition and excitation may be a general mechanism enabling sequence generation in other circuits.


Acute limb ischemia due to ergotism.
Acute ischemia of an extremity potentially threatens limb loss and occasionally the life of the patient. We are reporting two cases of extremity ischemia secondary to ergot poisoning. The first patient was a 60 years old woman, who presented with a 15 days history of ischemia of the left arm with gangrene of the fingers and pain in the resting right hand for one day. Right brachial artery catheterization showed severe spasm of the artery which was resolved by passage of the inflated balloon catheter. She underwent amputation for gangrene of the left hand. The second patient presented with bilateral symmetrical ischemia of the lower extremities which improved upon withdrawal of the ergot containing medicine. She responded to nifedipine.


Effects of low-concentrations of simazine on early life stages of common carp (Cyprinus carpio L.).
The aim of this study is to assess the toxicity of simazine in different developmental stages of common carp (Cyprinus carpio) on the basis of mortality, early ontogeny, occurrence of morphological anomalies, growth rate, and Fulton's condition factor during and at the conclusion of the test. The toxicity tests were performed on carp according to OECD 210 methodologies. The developmental stages of carp were exposed to simazine at four concentrations, 0.06, (reported concentration in Czech rivers), 60, 600, and 3000 µg/l for 36 days and compared to carp in a non-treated control group. Simazine in concentration 0.06 µg/l had no effect on early life stages of carp. Simazine in concentration 600 and 3000 µg/l caused decrease of mass and total length of carp. Fish exposed to three highest levels of simazine showed alteration of tubular system of caudal kidney. On the basis of histopatological changes the values of LOEC = 60 µg/l, NOEC = 0.06 µg/l for simazine were estimated. Chronic simazine exposure of early-life stages of common carp affected their growth rate, and histology. Some of the changes were observed only at higher exposures (600, 3000 µg/l), but change founded in caudal kidney was affected in fish exposed to the second lowest concentration tested (i.e., 60 µg/l), which is about 10 µg/l higher than reported in Colorado rivers in recent years. Concentrations of simazine in World rivers have been reported to generally vary in the range 0.0003-49.20 µg/l.


Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance.
Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental origin, or due to maternal effects reflecting the maternal genome's influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1meta-analysis = 2.4, P = 1.0 x 10-36), we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10-8). Our data point to two independent and additive effects of FLG mutations: i) carrying a mutation and ii) having a mutation carrier mother. The maternal genotype effect was independent of mutation inheritance and can be seen as a non-genetic transmission of a genetic effect. The FLG maternal effect was observed only when mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels), suggesting that FLG mutation-induced systemic immune responses in the mother may influence AD risk in the child. Notably, the maternal effect reported here was stronger than most common genetic risk factors for AD recently identified through genome-wide association studies (GWAS). Our study highlights the power of family-based studies in the identification of new etiological mechanisms and reveals, for the first time, a direct influence of the maternal genotype on the offspring's susceptibility to a common human disease.


A molecular basis for the anti-inflammatory and anti-fibrosis properties of cannabidiol.
Cannabidiol (CBD) is considered a non-psychoactive, antioxidant, and anti-inflammatory compound derived from the Cannabis sativa plant. There are various reports on the versatile function of CBD, including ameliorating chronic inflammation and fibrosis formation in several tissue types. However, only a hand full of studies have proposed or provided a molecular justification for the beneficial properties of this Phyto-compound. This review focused on the anti-inflammation and anti-fibrotic effects of CBD based on modulating the associated chemokines/cytokines and receptor-mediated pathways. We also highlighted the regulatory impact of CBD on reactive oxygen species (ROS) producing-NADPH oxidase (Nox), and ROS scavenging-superoxide dismutase (SOD) enzymes. Although CBD has a low affinity to Cannabinoid receptors 1 and 2 (CB1 and CB2 ), we reported on the activation of these receptors by other CBD analogs, and CBD on non-CBD receptors. CBD downregulates pro-inflammatory and pro-fibrotic chemokines/cytokines by acting as direct or indirect agonists of Adenosine A2A /equilibrative nucleoside transporter receptors, Peroxisome proliferator-activated receptor gamma, and Transient receptor potential vanilloid receptors or channels, and as an antagonist of GPR55 receptors. CBD also caused the reduction and enhancement of the ROS producing, Nox and ROS-scavenging, SOD enzyme activities, respectively. This review thus recommends the continued study of CBD's molecular mechanism in treating established and emerging inflammatory and fibrosis-related diseases.


Evaluation of antibiotic prescribing pattern in pediatrics in a tertiary care hospital.
The irrational use of antibiotics is a global issue and it can lead to morbidity, mortality, and increased health care costs. Hence, proper use of antibiotics is imperative and should be included in the pharmaceutical care plan. The objective of this study was to evaluate the prescribing pattern of antibiotics for children using WHO core prescribing indicators. A prospective, observational study was carried for 6 months in the pediatric department at a tertiary care hospital, Pune. The WHO prescribing indicators were used to evaluate the prescriptions, and the ideal WHO range was considered as a determining factor for rational prescription. A total of 302 patients were included in the study, with a mean patient age of 4.92 ± 4 years. The average number of drugs per encounter was 6.12 (WHO standard is less than 2). The percentage of antibiotics prescribed was 26.3% with an average of 1.63 antibiotics per prescription. Of the 493 antibiotics, 85.59% were injectable which is higher than the WHO standard of 13.4-24.1%. A near-optimal value of 99.59% antibiotics was prescribed from the hospital formulary which is similar to WHO standards, and the antibiotics prescribed with generic names were 25.76%. The most common class of antibiotics prescribed were cephalosporins and penicillins. Polypharmacy, high injectable use, and non-adherence to generic prescription were common in our tertiary care center. Continuous audits, training, and new treatment protocols are recommended.


Anterior-medial thalamic lesions in dementia: frequent, and volume dependently associated with sudden cognitive decline.
The anterior-medial thalamus (AMT), which is associated with memory processing, is severely affected by Alzheimer's disease pathology and, when damaged, can be the sole cause of dementia. To assess the frequency of magnetic resonance imaging (MRI) hyperintensities affecting the AMT, and their relationship with sudden cognitive decline. 205 consecutive participants from a university cognitive neurology clinic underwent clinical evaluation, neuropsychological testing and quantitative MRI. AMT hyperintensities >5 mm3 occurred in 0 of 34 normal controls but were found in 5 of 30 (17%) participants with cognitive impairment with no dementia (CIND), 9 of 109 (8%) patients with probable Alzheimer's disease, 7 of 17 (41%) with mixed disease and 8 of 15 (53%) with probable vascular dementia (VaD). AMT hyperintensities occurred more often in participants with stepwise decline than in those with slow progression (chi2 = 31.7; p<0.001). Of the 29 people with AMT hyperintensities, those with slow progression had smaller medial temporal width (p<0.001) and smaller anterior-medial thalamic hyperintensities (p<0.001). In a logistic regression model, both variables were significant, and the pattern of decline was correctly classified in 86% of the sample (Cox and Snell R2 = 0.56; p<0.001). Those with AMT hyperintensities >55 mm3 were likely to have stepwise decline in cognitive function regardless of medial temporal lobe width; in contrast, those with smaller AMT hyperintensities showed a stepwise decline only in the absence of medial temporal lobe atrophy. All patients with VaD had left-sided AMT hyperintensities, whereas those with CIND had right-sided AMT hyperintensities. AMT hyperintensities >55 mm3 probably result in symptomatic decline, whereas smaller lesions may go unrecognised by clinicians and radiologists. Only half of those with AMT hyperintensities had diagnoses of VaD or mixed disease; the other AMT hyperintensities occurred in patients diagnosed with Alzheimer's disease or CIND. These silent hyperintensities may nevertheless contribute to cognitive dysfunction. AMT hyperintensities may represent a major and under-recognised contributor to cognitive impairment.


Trehalose: an intriguing disaccharide with potential for medical application in ophthalmology.
Trehalose is a naturally occurring disaccharide comprised of two molecules of glucose. The sugar is widespread in many species of plants and animals, where its function appears to be to protect cells against desiccation, but is not found in mammals. Trehalose has the ability to protect cellular membranes and labile proteins against damage and denaturation as a result of desiccation and oxidative stress. Trehalose appears to be the most effective sugar for protection against desiccation. Although the exact mechanism by which trehalose protects labile macromolecules and lipid membranes is unknown, credible hypotheses do exist. As well as being used in large quantities in the food industry, trehalose is used in the biopharmaceutical preservation of labile protein drugs and in the cryopreservation of human cells. Trehalose is under investigation for a number of medical applications, including the treatment of Huntington's chorea and Alzheimer's disease. Recent studies have shown that trehalose can also prevent damage to mammalian eyes caused by desiccation and oxidative insult. These unique properties of trehalose have thus prompted its investigation as a component in treatment for dry eye syndrome. This interesting and unique disaccharide appears to have properties which may be exploited in ophthalmology and other disease states.


On the rationale and interpretation of the Farm Scale Evaluations of genetically modified herbicide-tolerant crops.
Farmland biodiversity and food webs were compared in conventional and genetically modified herbicide-tolerant (GMHT) crops of beet (Beta vulgaris L.), maize (Zea mays L.) and both spring and winter oilseed rape (Brassica napus L.). GMHT and conventional varieties were sown in a split-field experimental design, at 60-70 sites for each crop, spread over three starting years beginning in 2000. This paper provides a background to the study and the rationale for its design and interpretation. It shows how data on environment, field management and the biota are used to assess the current state of the ecosystem, to define the typical arable field and to devise criteria for selecting, sampling and auditing experimental sites in the Farm Scale Evaluations. The main functional and taxonomic groups in the habitat are ranked according to their likely sensitivity to GMHT cropping, and the most responsive target organisms are defined. The value of the seedbank as a baseline and as an indicator of historical trends is proposed. Evidence from experiments during the twentieth century is analysed to show that large changes in field management have affected sensitive groups in the biota by ca. 50% during a year or short run of years--a figure against which to assess any positive or negative effects of GMHT cropping. The analysis leads to a summary of factors that were, and were not, examined in the first 3 years of the study and points to where modelling can be used to extrapolate the effects to the landscape and the agricultural region.


Alu elements in primates are preferentially lost from areas of high GC content.
The currently-accepted dogma when analysing human Alu transposable elements is that 'young' Alu elements are found in low GC regions and 'old' Alus in high GC regions. The correlation between high GC regions and high gene frequency regions make this observation particularly difficult to explain. Although a number of studies have tackled the problem, no analysis has definitively explained the reason for this trend. These observations have been made by relying on the subfamily as a proxy for age of an element. In this study, we suggest that this is a misleading assumption and instead analyse the relationship between the taxonomic distribution of an individual element and its surrounding GC environment. An analysis of 103906 Alu elements across 6 human chromosomes was carried out, using the presence of orthologous Alu elements in other primate species as a proxy for age. We show that the previously-reported effect of GC content correlating with subfamily age is not reflected by the ages of the individual elements. Instead, elements are preferentially lost from areas of high GC content over time. The correlation between GC content and subfamily may be due to a change in insertion bias in the young subfamilies. The link between Alu subfamily age and GC region was made due to an over-simplification of the data and is incorrect. We suggest that use of subfamilies as a proxy for age is inappropriate and that the analysis of ortholog presence in other primate species provides a deeper insight into the data.


Imaging of mitochondrial and non-mitochondrial responses in cultured rat hippocampal neurons exposed to micromolar concentrations of TMRM.
Tetramethylrhodamine methyl ester (TMRM) is a fluorescent dye used to study mitochondrial function in living cells. Previously, we reported that TMRM effectively labeled mitochondria of neurons deep within mouse brain slices. Use of micromolar concentration of dye, which was required to get sufficient staining for two-photon imaging, resulted in typical fluctuations of TMRM. With prolonged exposure, we recorded additional responses in some neurons that included slow oscillations and propagating waves of fluorescence. (Note: We use the terms "fluctuation" to refer to a change in the fluorescent state of an individual mitochondrion, "oscillation" to refer to a localized change in fluorescence in the cytosol, and "wave" to refer to a change in cytosolic fluorescence that propagated within a cell. Use of these terms does not imply any underlying periodicity.) In this report we describe similar results using cultured rat hippocampal neurons. Prolonged exposure of cultures to 2.5 µM TMRM produced a spontaneous increase in fluorescence in some neurons, but not glial cells, after 45-60 minutes that was followed by slow oscillations, waves, and eventually apoptosis. Spontaneous increases in fluorescence were insensitive to high concentrations of FCCP (100 µM) and thapsigargin (10 µM) indicating that they originated, at least in part, from regions outside of mitochondria. The oscillations did not correlate with changes in intracellular Ca(2+), but did correlate with differences in fluorescence lifetime of the dye. Fluorescence lifetime and one-photon ratiometric imaging of TMRM suggested that the spontaneous increase and subsequent oscillations were due to movement of dye between quenched (hydrophobic) and unquenched (hydrophilic) compartments. We propose that these movements may be correlates of intracellular events involved in early stages of apoptosis.


Melatonin improves uterine-conceptus interaction via regulation of SIRT1 during early pregnancy.
Melatonin has been shown to improve in vitro fertilization and offspring survival after bacterial infection, but its role in regulating maternal-fetal communication during early pregnancy has not been investigated. Results of this study demonstrated expression of abundant melatonin receptors in conceptus and endometrium during early pregnancy. In gilts, expression of melatonin receptor 1A (MTNR1A or MT1) and melatonin receptor 1B (MTNR1B or MT2) increased in trophectoderm (Tr) and uterine luminal epithelium (LE) with advancing days during early pregnancy in a different manner. Melatonin increased proliferation and migration of porcine trophectoderm (pTr) cell, the percent pTr cells in the G2 phase of the cell cycle, and the expression of implantation-related genes by pTr cells and endometrial luminal epithelium (pLE). Melatonin also attenuated the production of LPS-induced pro-inflammatory cytokines and tunicamycin-induced endoplasmic reticulum (ER) stress-sensing proteins. The expression of sirtuin 1 (SIRT1) as a potential target of melatonin increased between Days 9 and 14 of gestation. Co-treatment with SIRT1 inhibitor EX527 and melatonin restored cell-cell interactions through PI3K and MAPK signaling. Knockdown of SIRT1 decreased the expression of implantation-related genes, as well as migration of pTr and pLE cells. The expression of microRNAs regulated by SIRT1 was suppressed in response to melatonin. Furthermore, melatonin significantly increased lipopolysaccharide (LPS)-reduced fertilization and embryogenesis in zebrafish model. These results suggest that melatonin may improve the uterine-conceptus interactions via the regulation of SIRT1 during early pregnancy.


Elevation of endocannabinoid levels in the ventrolateral periaqueductal grey through inhibition of fatty acid amide hydrolase affects descending nociceptive pathways via both cannabinoid receptor type 1 and transient receptor potential vanilloid type-1 receptors.
In the ventrolateral periaqueductal gray (PAG), activation of excitatory output neurons projecting monosynaptically to OFF cells in the rostral ventromedial medulla (RVM) causes antinociceptive responses and is under the control of cannabinoid receptor type-1 (CB1) and vanilloid transient receptor potential vanilloid type 1 (TRPV1) receptors. We studied in healthy rats the effect of elevation of PAG endocannabinoid [anandamide and 2-arachidonoylglycerol (2-AG)] levels produced by intra-PAG injections of the inhibitor of fatty acid amide hydrolase URB597 [cyclohexylcarbamic acid-3'-carbamoyl-biphenyl-3-yl ester] on 1) nociception in the "plantar test" and 2) spontaneous and tail-flick-related activities of RVM neurons. Depending on the dose or time elapsed since administration, URB597 (0.5-2.5 nmol/rat) either suppressed or increased thermal nociception via TRPV1 or CB1 receptors, respectively. TRPV1 or cannabinoid receptor agonists capsaicin (6 nmol) and (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3,-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate [WIN55,212-2 (4 nmol)] also suppressed or enhanced nociception, respectively. URB597 dose dependently enhanced PAG anandamide and 2-AG levels, with probable subsequent activation of TRPV1/CB1 receptors and only CB1 receptors, respectively. The TRPV1-mediated antinociception and CB1-mediated nociception caused by URB597 correlated with enhanced or reduced activity of RVM OFF cells, suggesting that these effects occur via stimulation or inhibition of excitatory PAG output neurons, respectively. Accordingly, several ventrolateral PAG neurons were found by immunohistochemistry to coexpress TRPV1 and CB1 receptors. Finally, at the highest doses tested, URB597 (4 nmol/rat) and, as previously reported, WIN55,212-2 (25-100 nmol) also caused CB(1)-mediated analgesia, correlating with stimulation (possibly disinhibition) of RVM OFF cells. Thus, endocannabinoids affect the descending pathways of pain control by acting at either CB1 or TRPV1 receptors in healthy rats.


Screening of pesticide residues in soil and water samples from agricultural settings.
The role of agricultural practices in the selection of insecticide resistance in malaria vectors has so far been hypothesized without clear evidence. Many mosquito species, Anopheles gambiae in particular, lay their eggs in breeding sites located around agricultural settings. There is a probability that, as a result of farming activities, insecticide residues may be found in soil and water, where they exercise a selection pressure on the larval stage of various populations of mosquitoes. To confirm this hypothesis, a study was conducted in the Republic of Benin to assess the environmental hazards which can be generated from massive use of pesticides in agricultural settings. Lacking an HPLC machine for direct quantification of insecticide residues in samples, this investigation was performed using indirect bioassays focussed on the study of factors inhibiting the normal growth of mosquito larvae in breeding sites. The speed of development was monitored as well as the yield of rearing An. gambiae larvae in breeding sites reconstituted with water and soil samples collected in agricultural areas known to be under pesticide pressure. Two strains of An. gambiae were used in this indirect bioassay: the pyrethroid-susceptible Kisumu strain and the resistant Ladji strain. The key approach in this methodology is based on comparison of the growth of larvae in test and in control breeding sites, the test samples having been collected from two vegetable farms. Results obtained clearly show the presence of inhibiting factors on test samples. A normal growth of larvae was observed in control samples. In breeding sites simulated by using a few grams of soil samples from the two vegetable farms under constant insecticide treatments (test samples), a poor hatching rate of Anopheles eggs coupled with a retarded growth of larvae and a low yield of adult mosquitoes from hatched eggs, was noticed. Toxic factors inhibiting the hatching of anopheles eggs and the growth of larvae are probably pesticide residues from agricultural practices. Samples used during this indirect assay have been stored in the laboratory and will be analysed with HPLC techniques to confirm hypothesis of this study and to identify the various end products found in soil and water samples from agricultural settings under pesticide pressure.


Interpersonal multisensory stimulation reduces the overwhelming distracting power of self-gaze: psychophysical evidence for 'engazement'.
One's own face and gaze are never seen directly but only in a mirror. Yet, these stimuli capture attention more powerfully than others' face and gaze, suggesting the self is special for brain and behavior. Synchronous touches felt on one's own and seen on the face of others induce the sensation of including others in one's own face (enfacement). We demonstrate that enfacement may also reduce the overwhelming distracting power of self-gaze. This effect, hereafter called 'engazement', depends on the perceived physical attractiveness and inner beauty of the pair partner. Thus, we highlight for the first time the close link between enfacement and engazement by showing that changes of the self-face representation induced by facial visuo-tactile stimulation extend to gaze following, a separate process likely underpinned by different neural substrates. Moreover, although gaze following is a largely automatic, engazement is penetrable to the influence of social variables, such as positive interpersonal perception.


The native bacterioplankton community in the central baltic sea is influenced by freshwater bacterial species.
The Baltic Sea is one of the largest brackish environments on Earth. Despite extensive knowledge about food web interactions and pelagic ecosystem functioning, information about the bacterial community composition in the Baltic Sea is scarce. We hypothesized that due to the eutrophic low-salinity environment and the long water residence time (>5 years), the bacterioplankton community from the Baltic proper shows a native "brackish" composition influenced by both freshwater and marine phylotypes. The bacterial community composition in surface water (3-m depth) was examined at a single station throughout a full year. Denaturing gradient gel electrophoresis (DGGE) showed that the community composition changed over the year. Further, it indicated that at the four extensive samplings (16S rRNA gene clone libraries and bacterial isolates from low- and high-nutrient agar plates and seawater cultures), different bacterial assemblages associated with different environmental conditions were present. Overall, the sequencing of 26 DGGE bands, 160 clones, 209 plate isolates, and 9 dilution culture isolates showed that the bacterial assemblage in surface waters of the central Baltic Sea was dominated by Bacteroidetes but exhibited a pronounced influence of typical freshwater phylogenetic groups within Actinobacteria, Verrucomicrobia, and Betaproteobacteria and a lack of typical marine taxa. This first comprehensive analysis of bacterial community composition in the central Baltic Sea points to the existence of an autochthonous estuarine community uniquely adapted to the environmental conditions prevailing in this brackish environment.


Cationic dynamic covalent polymers for gene transfection.
Dynamic covalent polymers are materials formed by reversible covalent bonds and non-covalent interactions through an adaptive constitutional dynamic chemistry. The implementation of dynamic covalent polymers in gene delivery has recently emerged due to their responsive and adaptive features. Indeed, such an approach offers the alluring promise of discovering optimal delivery vectors self-fitted to their nucleic acid cargos and responsive to environmental changes (e.g. pH changes or the presence of a biomolecular target). This review will discuss more precisely the structural features of the molecular building blocks used so far, the architecture of the resulting dynamic covalent polymers from linear to 2D and 3D, and the covalent and supramolecular self-assembly processes at play in nucleic acid recognition and delivery, showcasing in particular the very few examples of adaptive self-assembly of dynamic covalent polymers templated by nucleic acids and responsive to the presence of biomolecular targets found in cell membranes that facilitate cell entry.


Enhancement of irradiation effects on cancer cells by cross-linked dextran-coated iron oxide (CLIO) nanoparticles.
We investigated iron oxide nanoparticles with two different surface modifications, dextran coating and cross-linked dextran coating, showing that their different internalization affects their capability to enhance radiation damage to cancer cells. The internalization was monitored with an ultrahigh resolution transmission x-ray microscope (TXM), indicating that the differences in the particle surface charge play an essential role and dominate the particle-cell interaction. We found that dextran-coated iron oxide nanoparticles cannot be internalized by HeLa and EMT-6 cells without being functionalized with amino groups (the cross-linked dextran coating) that modify the surface potential from -18 mV to 13.4 mV. The amount of cross-linked dextran-coated iron oxide nanoparticles uptaken by cancer cells reached its maximum, 1.33 x 10(9) per HeLa cell, when the co-culture concentration was 40 microg Fe mL(-1) or more. Standard tests indicated that these internalized nanoparticles increased the damaging effects of x-ray irradiation, whereas they are by themselves biocompatible. These results could lead to interesting therapy applications; furthermore, iron oxide also produces high contrast for magnetic resonance imaging (MRI) in the diagnosis and therapy stages.


Groundwater chemistry and arsenic mobilization in the Holocene flood plains in south-central Bangladesh.
A comparative study of arsenic enrichment in the Bengal Delta (BD) was carried out in three alluvial aquifers in south-central Bangladesh. Investigated sites included Sonargaon in Narayanganj, Chandina in Comilla and Sirajdikhan in Munshiganj districts. At all sites samples from different depths were collected, and water chemistry and redox status vs. depth trends were determined. The concentrations of DOC and HCO(3)(-) were highest at Sirajdikhan site, while at the Sonargaon and Chandina sites the concentrations were lower. On the contrary, the NH(4)(+) concentration was high at the Chandina site as compared to the other sites. There was a good match between dissolved As and Fe at the Sirajdikhan and Sonargaon sites, but not at the Chandina site. The dissolved aqueous concentration of Mn was low at the Chandina site, which suggested that the Mn(IV) redox buffering step was missing. Speciation modeling indicated a possibility of siderite precipitation at all sites, but precipitation of rhodochrosite only at the Sonargaon and Sirajdikhan sites. At the Sirajdikhan site, the log P(CO2) values were very high (-1.37), which revealed the production of CO(2) in redox processes. Principal component analysis (PCA) indicated an impact of sea water and redox status of different samples. These results suggest that the dissolved As is de-coupled from dissolved Mn because when released, As is re-adsorbed onto the Fe(III) minerals in solid phase, as well as from dissolved Fe when precipitation of Fe(II) minerals controls the aqueous concentrations of Fe. In addition, several other concurrent redox processes may exert kinetic constraints depending on refractory characteristics of Fe(III) minerals.