Determinants of nurses' willingness to receive vaccines: Application of the health belief model.
To assess the willingness of nurses to receive vaccines as recommended by Taiwan's "Immunization Recommendations for Healthcare Personnel" (IRHCP), as well as the factors associated with their willingness. Immunisation for healthcare personnel (HCP) is a means of reducing pathogen transmission. Also, vaccinating HCP reduces personnel and labour costs during an epidemic. A cross-sectional study was conducted. A self-administered questionnaire survey targeting nurses working in various service units at three hospitals was used. In total, 413 nurses completed the questionnaire. The main outcome measure was the willingness to receive vaccines recommended by the IRHCP, and the variables we assessed included knowledge regarding the IRHCP, individual perceptions (perceived risk of contracting the infection, perceived severity of the infection and perceived transmissibility after disease onset), perceived benefits and barriers to the vaccination, cues to the vaccination and demographics. This study followed the STROBE checklist for reporting this study. The willingness of nurses to receive vaccines recommended by the IRHCP was high; the highest level of willingness was for the hepatitis B vaccine. The nurses' willingness to receive various vaccines recommended by the IRHCP was predicted by the knowledge regarding the IRHCP and perceived transmissibility after disease onset. Except the diphtheria-tetanus-acellular pertussis vaccine, perceived benefits and perceived barriers were also predictors of the willingness to receive vaccines. Our results showed that interventions focusing on increasing the knowledge regarding the IRHCP and perceived transmissibility after disease onset, emphasising the benefits of the vaccination and reducing the perceived barriers to the vaccination are needed to increase nurses' willingness to receive vaccines. It is suggested using health education courses and mass media broadcasts at the individual and societal levels to raise awareness regarding the benefits of vaccines and enhance nurse' confidence in vaccination programs.


Global Plastic Pollution Observation System to Aid Policy.
Plastic pollution has become one of the most pressing environmental challenges and has received commensurate widespread attention. Although it is a top priority for policymakers and scientists alike, the knowledge required to guide decisions, implement mitigation actions, and assess their outcomes remains inadequate. We argue that an integrated, global monitoring system for plastic pollution is needed to provide comprehensive, harmonized data for environmental, societal, and economic assessments. The initial focus on marine ecosystems has been expanded here to include atmospheric transport and terrestrial and freshwater ecosystems. An earth-system-level plastic observation system is proposed as a hub for collecting and assessing the scale and impacts of plastic pollution across a wide array of particle sizes and ecosystems including air, land, water, and biota and to monitor progress toward ameliorating this problem. The proposed observation system strives to integrate new information and to identify pollution hotspots (i.e., production facilities, cities, roads, ports, etc.) and expands monitoring from marine environments to encompass all ecosystem types. Eventually, such a system will deliver knowledge to support public policy and corporate contributions to the relevant United Nations (UN) Sustainable Development Goals (SDGs).


Fibromyalgia in patients with irritable bowel syndrome. An association with the severity of the intestinal disorder.
Fibromyalgia (FM) syndrome and irritable bowel syndrome (IBS) are functional disorders in which altered somatic and or visceral perception thresholds have been found. The aim of this study was to evaluate the prevalence of FM in a group of patients with IBS and the possible association of FM with patterns and severity of the intestinal disorder. One hundred thirty consecutive IBS patients were studied. The IBS was divided into four different patterns according to the predominant bowel symptom and into three levels of severity using a functional severity index. All patients underwent rheumatological evaluation for number of positive tender points, number of tender and swollen joints, markers of inflammation, and presence of headache and weakness. Moreover, patients' assessments of diffuse pain, mood and sleep disturbance, anxiety, and fatigue were also measured on a visual analogue scale. The diagnosis of FM was made based on American College of Rheumatology classification criteria. Nonparametric tests were used for statistical analysis. Fibromyalgia was found in 20% of IBS patients. No statistical association was found between the presence of FM and the type of IBS but a significant association was found between the presence of FM and severity of the intestinal disorder. The presence of FM in IBS patients seems to be associated only with the severity of IBS. This result confirms previous studies on the association between the two syndromes.


Macrostylis metallicola spec. nov.-an isopod with geographically clustered genetic variability from a polymetallic-nodule area in the Clarion-Clipperton Fracture Zone.
The Clarion-Clipperton Fracture Zone (CCFZ) in the Northeast Central Pacific Ocean is a region of heightened scientific and public interest because of its wealth in manganese nodules. Due to a poor ecological understanding at the abyssal seafloor and limited knowledge of the organisms inhabiting this area, huge efforts in alpha taxonomy are required. To predict and manage potential hazards associated with future mining, taxonomy is an essential first step to grasp fundamental ecosystem traits, such as biogeographic patterns, connectivity, and the potential for post-impact recolonization. Amongst samples from the Global Sea Mineral Resources NV exploration area (EA) in the CCFZ an undescribed species of the isopod crustacean family Macrostylidae was discovered. Previously, it has been reported from two other nearby regions, the Institut Français de Recherche pour l'Exploitation de la Mer and BGR EAs. There it was one of the more widely distributed and abundant species of the benthic macrofauna and exhibited geographically structured populations. It nevertheless remained taxonomically undescribed so far. The new species is described by means of integrative taxonomy. Morphologically, macro photography, confocal microscopy, scanning electron microscopy and light microscopy were used to describe the species and to get first insights on its phylogenetic origin. Additionally, mitochondrial DNA markers were used to test the morphological allocation of the two dimorphic sexes and juvenile stages, to analyze geographic patterns of genetic differentiation, and to study intra-and inter-species relationships, also in light of previously published population genetics on this species. The new species, Macrostylis metallicola spec. nov., is a typical representative of Macrostylidae as recognizable from the fossosoma, prognathous cephalothorax, and styliform uropods. It can be morphologically distinguished from congeners by a combination of character states which include the autapomorphic shape of the first pleopod of the copulatory male. A sexual dimorphism, as expressed by a peculiar sequence of article length-width ratios of the male antennula, indicates a relationship with M. marionae Kniesz, Brandt & Riehl (2018) and M. longipes Hansen (1916) amongst other species sharing this dimorphism. Mitochondrial genetic markers point in a similar direction. M. metallicola appears to be amongst the more common and widely distributed components of the benthic macrofauna in this region which may suggest a resilience of this species to future mining activities because of its apparent potential for recolonization of impacted sites from adjacent areas of particular environmental interest. The genetic data, however, show geographic clustering of its genetic variability, pointing towards a limited potential for dispersal. Local extinction of populations could potentially not be compensated quickly and would mean a loss of genetic diversity of this species.


Autoantibodies in complex regional pain syndrome bind to a differentiation-dependent neuronal surface autoantigen.
Complex regional pain syndrome, which is characterised by pain and trophic disturbances, develops frequently after peripheral limb trauma. There is an increasing evidence of an involvement of the immune system in CRPS, and recently we showed that CRPS patients have autoantibodies against nervous system structures. Therefore we tested the sera of CRPS patients, neuropathy patients and healthy volunteers for surface-binding autoantibodies to primary cultures of autonomic neurons and differentiated neuroblastoma cell lines using flow cytometry. Thirteen of 30 CRPS patients, but none of 30 healthy controls and only one of the 20 neuropathy sera had specific surface binding to autonomic neurons (p<0.001). The majority of the sera reacted with both sympathetic and myenteric plexus neurons. Interestingly, 6/30 CRPS sera showed binding to undifferentiated SH-SY5Y neuroblastoma cells. However, differentiation of SH-SY5Y into a cholinergic phenotype induced a surface antigen, which is recognised by 60% of CRPS sera (18/30), but not by controls (p<0.001). Our data show that about 30-40% of CRPS patients have surface-binding autoantibodies against an inducible autonomic nervous system autoantigen. These data support an autoimmune hypothesis in CRPS patients. Further studies must elucidate origin and function of these autoantibodies in CRPS.


Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the Better Diabetes Diagnosis study.
We examined whether zinc transporter 8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (≥1 islet autoantibody) type 1 diabetic patients (n = 2,964, <18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%). Non-Swedes had less frequent ZnT8-WA (38%) than Swedes (50%), consistent with a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%). ZnT8-RA (57 and 58%, respectively) did not differ despite a higher frequency of CC (RR) genotypes in non-Swedes (63%) than Swedes (46%). We tested whether this inconsistency was due to HLA-DQ as 2/X (2/2; 2/y; y is anything but 2 or 8), which was a major genotype in non-Swedes (40%) compared with Swedes (14%). In the non-Swedes only, 2/X (2/2; 2/y) was negatively associated with ZnT8-WA and ZnT8-QA but not ZnT8-RA. Molecular simulation showed nonbinding of the relevant ZnT8-R peptide to DQ2, explaining in part a possible lack of tolerance to ZnT8-R. At diagnosis in non-Swedes, the presence of ZnT8-RA rather than ZnT8-WA was likely due to effects of HLA-DQ2 and the SLC30A8 CC (RR) genotypes.


Risk of cervical precancer and cancer among HIV-infected women with normal cervical cytology and no evidence of oncogenic HPV infection.
US cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) results who test negative for oncogenic human papillomavirus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown. To determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV. Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional US cohort of the Women's Interagency HIV Study, between October 1, 2001, and September 30, 2002, with follow-up through April 30, 2011. Semiannual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using polymerase chain reaction. The primary analysis was truncated at 5 years of follow-up. Five-year cumulative incidence of cervical precancer and cancer. No oncogenic HPV was detected in 369 (88% [95% CI, 84%-91%]) HIV-infected women and 255 (91% [95% CI, 88%-94%]) HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women, 2 cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500 cells/μL or greater. Histologic data were obtained from 4 of the 6 clinical sites. There were 6 cases of CIN-2+ in 145 HIV-uninfected women (cumulative incidence, 5% [95% CI, 1%-8%]) and 9 cases in 219 HIV-infected women (cumulative incidence, 5% [95% CI, 2%-8%]). This included 1 case of CIN-2+ in 44 oncogenic HPV-negative HIV-infected women with CD4 cell count less than 350 cells/μL (cumulative incidence, 2% [95% CI, 0%-7%]), 1 case in 47 women with CD4 cell count of 350 to 499 cells/μL (cumulative incidence, 2% [95% CI, 0%-7%]), and 7 cases in 128 women with CD4 cell count of 500 cells/μL or greater (cumulative incidence, 6% [95% CI, 2%-10%]). One HIV-infected and 1 HIV-uninfected woman had CIN-3, but none had cancer. The 5-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.


Enhanced text spacing improves reading performance in individuals with macular disease.
The search by many investigators for a solution to the reading problems encountered by individuals with no central vision has been long and, to date, not very fruitful. Most textual manipulations, including font size, have led to only modest gains in reading speed. Previous work on spatial integrative properties of peripheral retina suggests that 'visual crowding' may be a major factor contributing to inefficient reading. Crowding refers to the fact that juxtaposed targets viewed eccentrically may be difficult to identify. The purpose of this study was to assess the combined effects of line spacing and word spacing on the ability of individuals with age-related macular degeneration (ARMD) to read short passages of text that were printed with either high (87.5%) or low contrast (17.5%) letters. Low contrast text was used to avoid potential ceiling effects and to mimic a possible reduction in letter contrast with light scatter from media opacities. For both low and high contrast text, the fastest reading speeds we measured were for passages of text with double line and double word spacing. In comparison with standard single spacing, double word/line spacing increased reading speed by approximately 26% with high contrast text (p < 0.001), and by 46% with low contrast text (p < 0.001). In addition, double line/word spacing more than halved the number of reading errors obtained with single spaced text. We compare our results with previous reading studies on ARMD patients, and conclude that crowding is detrimental to reading and that its effects can be reduced with enhanced text spacing. Spacing is particularly important when the contrast of the text is reduced, as may occur with intraocular light scatter or poor viewing conditions. We recommend that macular disease patients should employ double line spacing and double-character word spacing to maximize their reading efficiency.


Genotypic diversity of anaerobic isolates from bloodstream infections.
Accurate species determination for anaerobes from blood culture bottles has become increasingly important with the reemergence of anaerobic bacteremia and prevalence of multiple-drug-resistant microorganisms. Our knowledge of the taxonomical diversity of anaerobes that cause bloodstream infections is extremely limited, because identification historically has relied on conventional methods. Over a 5-year period, we profiled anaerobic bacteremia at a large tertiary care hospital with 16S rRNA gene sequencing to gain a better understanding of the taxonomical diversity of the bacteria. Of 316 isolates, 16S rRNA gene sequencing and phylogenetic analysis identified 316 (100%) to the genus or taxonomical group level and 289 (91%) to the species level. Conventional methods identified 279 (88%) to the genus level and 208 (66%) to the species level; 75 (24%) were misidentified at the species level, and 33 (10%) results were inconclusive. High intragenus variability was observed for Bacteroides and Clostridium species, and high intraspecies variability was observed for Bacteroides thetaiotaomicron and Fusobacterium nucleatum. Sequence-based identification has potential benefits in comparison to conventional methods, because it more accurately characterizes anaerobes within taxonomically related clusters and thereby may enable better correlation with specific clinical syndromes and antibiotic resistance patterns.


Biometrics for electronic health records.
Securing electronic health records, in scenarios in which the provision of care services is share among multiple actors, could become a complex and costly activity. Correct identification of patients and physician, protection of privacy and confidentiality, assignment of access permissions for healthcare providers and resolutions of conflicts rise as main points of concern in the development of interconnected health information networks. Biometric technologies have been proposed as a possible technological solution for these issues due to its ability to provide a mechanism for unique verification of an individual identity. This paper presents an analysis of the benefit as well as disadvantages offered by biometric technology. A comparison between this technology and more traditional identification methods is used to determine the key benefits and flaws of the use biometric in health information systems. The comparison as been made considering the viability of the technologies for medical environments, global security needs, the contemplation of a share care environment and the costs involved in the implementation and maintenance of such technologies. This paper also discusses alternative uses for biometrics technologies in health care environments. The outcome of this analysis lays in the fact that even when biometric technologies offer several advantages over traditional method of identification, they are still in the early stages of providing a suitable solution for a health care environment.


Ancient DNA reveals genetic stability despite demographic decline: 3,000 years of population history in the endemic Hawaiian petrel.
In the Hawaiian Islands, human colonization, which began approximately 1,200 to 800 years ago, marks the beginning of a period in which nearly 75% of the endemic avifauna became extinct and the population size and range of many additional species declined. It remains unclear why some species persisted whereas others did not. The endemic Hawaiian petrel (Pterodroma sandwichensis) has escaped extinction, but colonies on two islands have been extirpated and populations on remaining islands have contracted. We obtained mitochondrial DNA sequences from 100 subfossil bones, 28 museum specimens, and 289 modern samples to investigate patterns of gene flow and temporal changes in the genetic diversity of this endangered species over the last 3,000 years, as Polynesians and then Europeans colonized the Hawaiian Islands. Genetic differentiation was found to be high between both modern and ancient petrel populations. However, gene flow was substantial between the extirpated colonies on Oahu and Molokai and modern birds from the island of Lanai. No significant reductions in genetic diversity occurred over this period, despite fears in the mid-1900s that this species may have been extinct. Simulations show that even a decline to a stable effective population size of 100 individuals would result in the loss of only 5% of the expected heterozygosity. Simulations also show that high levels of genetic diversity may be retained due to the long generation time of this species. Such decoupling between population size and genetic diversity in long-lived species can have important conservation implications. It appears that a pattern of dispersal from declining colonies, in addition to long generation time, may have allowed the Hawaiian petrel to escape a severe genetic bottleneck, and the associated extinction vortex, and persist despite a large population decline after human colonization.


Anomalous modal structure in a waveguide with a photonic crystal core.
We analyze a dielectric waveguide with a photonic crystal core. Using constant frequency contour analysis, we show that the modal behavior of this structure is drastically different from that of a conventional slab waveguide. In particular, at a given frequency the lowest-order guided mode can have an odd symmetry or can have more than one nodal plane in its field distribution. Also, there exist several single-mode regions with a different modal profile in each region. Finally, a single-mode waveguide for the fundamental mode with a large core and strong confinement can be realized. All these behaviors are confirmed by our three-dimensional finite-difference time-domain simulations.


A written language intervention for at-risk second grade students: a randomized controlled trial of the process assessment of the learner lesson plans in a tier 2 response-to-intervention (RtI) model.
In a randomized controlled trial, 205 students were followed from grades 1 to 3 with a focus on changes in their writing trajectories following an evidence-based intervention during the spring of second grade. Students were identified as being at-risk (n=138), and then randomized into treatment (n=68) versus business-as-usual conditions (n=70). A typical group also was included (n=67). The writing intervention comprised Lesson Sets 4 and 7 from the Process Assessment of the Learner (PAL), and was conducted via small groups (three to six students) twice a week for 12 weeks in accordance with a response-to-intervention Tier 2 model. The primary outcome was the Wechsler Individual Achievement Test-II Written Expression Scale. Results indicated modest support for the PAL lesson plans, with an accelerated rate of growth in writing skills following treatment. There were no significant moderator effects, although there was evidence that the most globally impaired students demonstrated a more rapid rate of growth following treatment. These findings suggest the need for ongoing examination of evidence-based treatments in writing for young elementary students.


c-Jun N-terminal kinase contributes to aberrant retinoid signaling in lung cancer cells by phosphorylating and inducing proteasomal degradation of retinoic acid receptor alpha.
Retinoic acid (RA) is the ligand for nuclear RA receptors (RARs and RXRs) and is crucial for normal epithelial cell growth and differentiation. During malignant transformation, human bronchial epithelial cells acquire a block in retinoid signaling caused in part by a transcriptional defect in RARs. Here, we show that activation of c-Jun N-terminal kinase (JNK) contributes to RAR dysfunction by phosphorylating RARalpha and inducing degradation through the ubiquitin-proteasomal pathway. Analysis of RARalpha mutants and phosphopeptide mapping revealed that RARalpha residues Thr181, Ser445, and Ser461 are phosphorylated by JNK. Mutation of these residues to alanines prevented efficient ubiquitination of RARalpha and increased the stability of the protein. We investigated the importance of RARalpha phosphorylation by JNK as a mediator of retinoid resistance in lung cancer. Mice that develop lung cancer from activation of a latent K-ras oncogene had high intratumoral JNK activity and low RARalpha levels and were resistant to treatment with an RAR ligand. JNK inhibition in a human lung cancer cell line enhanced RARalpha levels, ligand-induced activity of RXR-RAR dimers, and growth inhibition by RA. These findings point to JNK as a key mediator of aberrant retinoid signaling in lung cancer cells.


Lessons for the new CMS innovation center from the Medicare health support program.
The Patient Protection and Affordable Care Act establishes a new Center for Medicare and Medicaid Innovation in the Centers for Medicare and Medicaid Services (CMS). The center is intended to enhance the CMS's role in promoting much-needed improvements in payment and service delivery. Lessons from the Medicare Health Support Program, a chronic care pilot program that ran between 2005 and 2008, illustrate the value of drawing on experience in planning for the center and future pilot programs. The lessons include the importance of strong leadership; collaboration and flexibility to foster innovation; receptivity of beneficiaries to care management; and the need for timely data on patients' status. The lessons also highlight pitfalls to be avoided in planning future pilot programs, such as flawed strategies for selecting populations to target when testing payment and service delivery reforms.


Induction of Hypopituitarism Following Ipilimumab/Nivolumab Therapy Followed by Radiation in the Treatment of Metastatic Scalp Melanoma.
Description Immune checkpoint inhibitors (ICI) are antagonistic antibodies that block specific immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. With FDA approval, the use of these checkpoint inhibitors has led to long-lasting tumor responses. However, by stimulating the immune system, checkpoint inhibitors can cause immune-related adverse events involving the endocrine organs, among others. Pituitary dysfunction (hypophysitis) leading to secondary adrenal insufficiency, or primary adrenal insufficiency caused by immune checkpoint inhibitors, have been documented. In this report, we present a case of a 70-year-old man with scalp melanoma with metastasis to the neck lymph nodes who remained asymptomatic 2 weeks after treatment completion with ipilimumab/nivolumab. However, he became lethargic, lost his appetite and was unable to perform activities of daily living following the initiation of radiation therapy to his neck. After hospitalization, he was found to have hyponatremia, hypocortisolism and hypopituitarism. He was treated with hydrocortisone, which lead to significant symptom improvement. His case suggests a dual-hit mechanism of injury to the pituitary caused by combined ICI and radiation therapies. Following ICI therapy, he was on the verge of pituitary dysfunction that fully materialized following a second insult. We suggest that for patients treated with ICIs, particularly with ipilimumab/nivolumab, a washout period may be considered before starting other forms of therapies, such as radiation therapy to the head/neck regions. Otherwise, prophylactic low dose corticosteroids may be initiated in cases where radiation therapy must not be delayed.


Expression of mutant bone morphogenetic protein receptor II worsens pulmonary hypertension secondary to pulmonary fibrosis.
Pulmonary fibrosis is often complicated by pulmonary hypertension (PH), and previous studies have shown a potential link between bone morphogenetic protein receptor II (BMPR2) and PH secondary to pulmonary fibrosis. We exposed transgenic mice expressing mutant BMPR2 and control mice to repetitive intraperitoneal injections of bleomycin for 4 weeks. The duration of transgene activation was too short for mutant BMPR2 mice to develop spontaneous PH. Mutant BMPR2 mice had increased right ventricular systolic pressure compared to control mice, without differences in pulmonary fibrosis. We found increased hypoxia-inducible factor (HIF)1-α stabilization in lungs of mutant-BMPR2-expressing mice compared to controls following bleomycin treatment. In addition, expression of the hypoxia response element protein connective tissue growth factor was increased in transgenic mice as well as in a human pulmonary microvascular endothelial cell line expressing mutant BMPR2. In mouse pulmonary vascular endothelial cells, mutant BMPR2 expression resulted in increased HIF1-α and reactive oxygen species production following exposure to hypoxia, both of which were attenuated with the antioxidant TEMPOL. These data suggest that expression of mutant BMPR2 worsens secondary PH through increased HIF activity in vascular endothelium. This pathway could be therapeutically targeted in patients with PH secondary to pulmonary fibrosis.


Human hepatocyte polyploidization kinetics in the course of life cycle.
The processes of polyploidization in normal human liver parenchyma from 155 individuals aged between 1 day and 92 years were investigated by Feulgen-DNA cytophotometry. It was shown that polyploid hepatocytes appear in individuals from 1 to 5 years old. Up to the age of 50 years the accumulation rate of binucleate and polyploid cells is very slow, but subsequently hepatocyte polyploidization is intensified, and in patients aged 86-92 years the relative number of cells with polyploid nuclei is about 27%. Only a few hepatocytes in the normal human liver reach 16C and 8C x 2 ploidy levels for mononucleate and binucleate cells respectively. Using a mathematical modeling method, it was shown that during postnatal liver growth the polyploidization process in human liver is similar to that in the rat, and that polyploid cells are formed mainly from binucleate cells. As in rats, prior to an increase in ploidy level, diploid human hepatocytes can pass several times through the usual mitotic cycles maintaining their initial ploidy level. After birth, only one in ten hepatocytes starting DNA synthesis enters the polyploidization process. At maturity about 60% of 2C-hepatocytes starting DNA synthesis divide by conventional mitosis, the rest dividing by acytokinetic mitosis leading to the formation of binucleate cells. During ageing the probability of hepatocyte polyploidization increases and in this period there are two polyploid or binucleate cells for every diploid dividing by conventional mitosis.


A roadmap for research on crassulacean acid metabolism (CAM) to enhance sustainable food and bioenergy production in a hotter, drier world.
Crassulacean acid metabolism (CAM) is a specialized mode of photosynthesis that features nocturnal CO2 uptake, facilitates increased water-use efficiency (WUE), and enables CAM plants to inhabit water-limited environments such as semi-arid deserts or seasonally dry forests. Human population growth and global climate change now present challenges for agricultural production systems to increase food, feed, forage, fiber, and fuel production. One approach to meet these challenges is to increase reliance on CAM crops, such as Agave and Opuntia, for biomass production on semi-arid, abandoned, marginal, or degraded agricultural lands. Major research efforts are now underway to assess the productivity of CAM crop species and to harness the WUE of CAM by engineering this pathway into existing food, feed, and bioenergy crops. An improved understanding of CAM has potential for high returns on research investment. To exploit the potential of CAM crops and CAM bioengineering, it will be necessary to elucidate the evolution, genomic features, and regulatory mechanisms of CAM. Field trials and predictive models will be required to assess the productivity of CAM crops, while new synthetic biology approaches need to be developed for CAM engineering. Infrastructure will be needed for CAM model systems, field trials, mutant collections, and data management.


A method for characterizing transition concertedness from polymer dynamics computer simulations.
A statistical method based on classifying the transitions among a set of dihedral angles within an "energy transfer window" is developed, and used to analyze Brownian (BD) and molecular dynamics (MD) simulations of the acyl chains in a lipid bilayer, and MD of neat hexadecane. It is shown for the BD simulation that when a transition of the dihedral angle in the center of the chain occurs, a transition of a particular next nearest neighbor (or angle 2-apart) will follow concertedly with a probability of approximately 0.10 within a time window of approximately 3 ps. The MD bilayer simulations, which are based on a more flexible model of the hydrocarbon chains, yield corresponding concerted transition probabilities of approximately 0.083 and window sizes of 1-2 ps. An analysis of angles 4-apart yields concerted transition probabilities of 0.03 and 0.04 for the BD and MD bilayer simulations, respectively, and window sizes close to those of the corresponding 2-apart cases. Statistical hypothesis testing very strongly rejects the assertion that these follower transitions are occurring at random. Similar analysis reveals marginal or no evidence of concertedness between 1-apart (nearest neighbor) and between 3-apart dihedral angle transitions. The pattern of concertedness for hexadecane is qualitatively similar to that of the lipid chains, although concertedness is somewhat stronger for the 3-apart transitions and somewhat weaker for those 4-apart. Finally, it is suggested that the diffusion of small solute molecules in membranes is better facilitated by nonconcerted transitions, which are associated with relatively large displacements of the chains, than by concerted transitions, which do little to change the chain shape.


Antagonism of endothelin action normalizes altered levels of VEGF and its signaling in the brain of stroke-prone spontaneously hypertensive rat.
Stroke-prone spontaneously hypertensive rats (SHRSP) often suffer from spontaneous stroke, in part, due to abnormalities in the cerebrovasculature. Here, we investigate the profile of key angiogenic factors and their basic signaling molecules in the brain of SHRSP during the age-dependent stages of hypertension. The profile of VEGF and its receptor, Flk-1, was dependent on age and stage of hypertension (i.e., down regulated at pre-hypertensive and malignant hypertensive stages, but up regulated at typical hypertensive stage), while that of its downstream components, pAkt and eNOS, were down regulated in a time-dependent manner in the frontal cortex of SHRSP compared to age-matched genetic control, normotensive WKY rats. On the other hand, the expression of endothelin-1 and its type A receptor (endothelin ETA receptor) were up regulated, depending on age and stage of hypertension. In contrast, levels of endothelin type B receptor were down regulated. The regional cerebral blood flow decreased during the development of malignant hypertension. Thus, subsequent experiments were designed to investigate whether endothelin-1 receptor antagonism, using endothelin-A/-B dual receptor antagonist SB209670, could normalize the molecular profile of these factors in SHRSP brain. Interestingly, blockage of endothelin-1 receptor restored to normal, levels of cerebral endothelin-1, endothelin ETA receptor and endothelin ETB receptor; VEGF and Flk-1; endothelial nitric oxide synthase (eNOS) and pAkt, in SHRSP, compared to age-matched WKY. Endothelin receptor blocker might be important to prevent the progression in the defect in VEGF and its angiogenic signaling cascade in the pathogenesis of hypertension-induced vascular remodeling in frontal cortex of SHRSP rats.


Medication Reconciliation in the Hospital: An Interactive Case-Based Session for Internal Medicine Residents.
Medication reconciliation is a complex process of creating and maintaining the most accurate medication list for a patient to help guide therapy. Done incorrectly, the process of medication reconciliation can lead to medical error and result in adverse events for patients. Medication reconciliation on inpatient medicine service is often done by internal medicine residents. However, published reports of educational interventions for residents are limited. We created a 1-hour session that was experiential, case based, and targeted to the level of a first-year resident. In total, 31 internal medicine residents completed the curriculum, which involved either a 1-hour classroom group activity or an individual virtual activity. The curriculum was evaluated using standard forms with qualitative feedback regarding learner satisfaction, pre- and postsession confidence survey, and pre- and postsession patient chart audits. Qualitative feedback demonstrated residents' positive experiences. There was no significant change in residents' confidence in portions of the medication reconciliation process. One month following the educational intervention, 100% of inpatient charts audited for review of the medication list were accurate, as compared to 67%-83% accuracy prior to the session. This novel case-based medication reconciliation teaching session, targeted at learners in an internal medicine residency, can easily be implemented at other institutions using the institution-specific electronic health record. The session was well received by residents, and we observed improved accuracy in the medication reconciliation process done by residents.


Relationships between legal and clinical factors among forensic hospital patients.
Recognizing that established relationships enhance understanding and therefore improve clinical intuition and inference, the authors examined clinical and legal characteristics of a legally and clinically heterogeneous population of maximum security forensic hospital patients (n = 380). Several findings serve to substantiate outcomes of previous studies of subgroups of offenders. Some new relationships among legal and clinical variables are established. The relationship between admission legal status and Axis I diagnosis is dependent upon the Axis II diagnosis. Those admitted for competency evaluations have the lowest percentage of psychotic diagnoses and the highest IQ. Kidnapers have the highest percentage of psychotic diagnoses and there is a relationship between previous incarceration and drug treatment refusal. The authors discuss clinical implications, generalizability, and the needs for further investigation.


Differences in the expression of pemphigus antigens during epidermal differentiation.
Epidermal desmogleins with molecular weights of 130/140 kDa (Dsg3 or PVA) and 150/160 kDa (Dsg1 or DGI) are recognized by autoantibodies from patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF), respectively. In order to understand the histogenesis of both types of pemphigus, we studied the expression patterns of Dsg1 and Dsg3 during stratification of cultured keratinocytes. Monolayers of cultured normal human keratinocytes demonstrated uniform intercellular staining with PV sera. The staining pattern was distinct from the focal staining with PF sera observed only in the stratified areas. Both Dsg1 and Dsg3 proteins and their mRNA were expressed by the monolayers, whereas no production of Dsg2 (HDGC) mRNA was found. The relative ratio of Dsg3 to the total desmogleins, as determined by density on immunoblotting, decreased as the cultured keratinocytes stratified. In the completely stratified keratinocytes cultured on collagen membrane, Dsg1 became predominant, with subsequent reduction of PV antigen expression. The relative decrease of Dsg3 (PVA) during epidermal differentiation might be responsible for the induction of suprabasal acantholysis in PV.


Disturbed functional connectivity of cortical activation during semantic discrimination in patients with schizophrenia and subjects at genetic high-risk.
Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca's area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca's area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca's area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.


Fluid intake and the risk of urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Results from previous studies investigating the association between fluid intake and urothelial cell carcinomas (UCC) are inconsistent. We evaluated this association among 233,236 subjects in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had adequate baseline information on water and total fluid intake. During a mean follow-up of 9.3 years, 513 first primary UCC occurred. At recruitment, habitual fluid intake was assessed by a food frequency questionnaire. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for energy intake, smoking status, duration of smoking and lifetime intensity of smoking. When using the lowest tertile of intake as reference, total fluid intake was not associated with risk of all UCC (HR 1.12; 95%CI 0.86-1.45, p-trend = 0.42) or with risk of prognostically high-risk UCC (HR 1.28; 95%CI 0.85-1.93, p-trend = 0.27) or prognostically low-risk UCC (HR 0.93; 95%CI 0.65-1.33, p-trend = 0.74). No associations were observed between risk of UCC and intake of water, coffee, tea and herbal tea and milk and other dairy beverages. For prognostically low-risk UCC suggestions of an inverse association with alcoholic beverages and of a positive association with soft drinks were seen. Increased risks were found for all UCC and prognostically low-risk UCC with higher intake of fruit and vegetable juices. In conclusion, total usual fluid intake is not associated with UCC risk in EPIC. The relationships observed for some fluids may be due to chance, but further investigation of the role of all types of fluid is warranted.


What Are the Risk Factors for Revision Surgery After Hip Arthroscopy for Femoroacetabular Impingement at 7-year Followup?
In recent years, surgical treatment of symptomatic femoroacetabular impingement (FAI) has been increasingly performed using arthroscopy. Bony pathomorphologies and damage to the labrum as well as cartilage defects can be addressed with comparable results to open surgery with overall less surgery-related complications. Despite the increasing importance of hip arthroscopy, however, reports on midterm clinical and radiographic outcomes and comparison to open surgical hip dislocation are scarce. (1) What are the clinical and radiographic outcomes at a mean 7-year followup; (2) what is the cumulative 7-year survivorship, using the endpoints of THA, progression of osteoarthritis according to Tönnis, or poor clinical outcome with a Merle d'Aubigné score of less than 15 points, of hips with symptomatic FAI treated arthroscopically; and (3) what factors were associated with revision surgery? Between 2003 and 2008 we performed a total of 62 arthroscopic procedures (60 patients) for FAI. For the same indication, we also performed 571 surgical hip dislocations during that time. Standardized treatment was femoral offset correction, acetabular rim trimming, or both and treatment of labral or chondral defects. An arthroscopic approach was generally used if the pathomorphology was located in the anterosuperior quadrant of the hip and was gradually used for more complex cases. We excluded 10 hips (10 patients) in which the standardized treatment was not achieved and no offset correction or acetabular rim trimming was performed. Of the remaining 52 hips (50 patients), 39 hips underwent isolated femoral offset correction, four hips isolated acetabular rim trimming, and nine hips both procedures. At a mean followup of 7 years (range, 5-11 years), the Merle d'Aubigné clinical score was obtained and plain radiographs were examined (Tönnis grade, heterotopic ossification, lateral center-edge [LCE] angle, acetabular index [AI], extrusion index, alpha angle, and pistol grip deformity). Cumulative survivorship was calculated according to Kaplan-Meier using conversion to THA, progression of osteoarthritis (one or more Tönnis grades), or poor clinical outcome (Merle d'Aubigné score < 15 points) as endpoints. Cox regression analysis was used to identify univariate factors associated with revision surgery. At last followup we detected a significant but possibly not clinically relevant increase in Merle d'Aubigné scores from preoperative levels to latest followup (14 ± 1 versus 16 ± 2, mean difference 2 points with a 95% confidence interval [95% CI] -3 to 7, p < 0.001). Six hips showed progression of osteoarthritis. Cumulative survivorship (hips free from conversion to THA, progression of osteoarthritis, or poor clinical outcome) of hips treated with hip arthroscopy for FAI at a mean followup of 7 years was 81% (95% CI, 68%-95%). Two patients (two hips, 4%) underwent THA at 7 and 9 years, respectively. An increased preoperative acetabular coverage (LCE angle, AI), increased offset in the superior portion of the femoral neck (pistol grip deformity), and a remaining pistol grip deformity postoperatively were associated with revision surgery. Any treatment of the labrum did not influence the outcome. Factors associated with failure could not be identified. In this series of patients with arthroscopic treatment of symptomatic FAI, hip arthroscopy resulted in an intact hip without progression of osteoarthritis and with a Merle d'Aubigné score of ≥ 15 points in 81% of patients at 7-year followup. Increased acetabular coverage and femoral pistol grip deformity were risk factors for revision surgery. Level IV, therapeutic study.


A palaeoequatorial ornithischian and new constraints on early dinosaur diversification.
Current characterizations of early dinosaur evolution are incomplete: existing palaeobiological and phylogenetic scenarios are based on a fossil record dominated by saurischians and the implications of the early ornithischian record are often overlooked. Moreover, the timings of deep phylogenetic divergences within Dinosauria are poorly constrained owing to the absence of a rigorous chronostratigraphical framework for key Late Triassic-Early Jurassic localities. A new dinosaur from the earliest Jurassic of the Venezuelan Andes is the first basal ornithischian recovered from terrestrial deposits directly associated with a precise radioisotopic date and the first-named dinosaur from northern South America. It expands the early palaeogeographical range of Ornithischia to palaeoequatorial regions, an area sometimes thought to be devoid of early dinosaur taxa, and offers insights into early dinosaur growth rates, the evolution of sociality and the rapid tempo of the global dinosaur radiation following the end-Triassic mass extinction, helping to underscore the importance of the ornithischian record in broad-scale discussions of early dinosaur history.


Characteristics of Orthopedic Publications in High-Impact General Medical Journals.
Orthopedic studies are occasionally published in high-impact general medical journals; these studies are often given high visibility and have significant potential to impact health care policy and inform clinical decision-making. The purpose of this review was to investigate the characteristics of operative orthopedic studies published in high-impact medical journals. The number of orthopedic studies published in high-impact medical journals is relatively low; however, these studies demonstrate methodological characteristics that may bias toward nonoperative treatment. Careful analysis and interpretation of orthopedic studies published in these journals is warranted. [Orthopedics. 2017; 40(3):e405-e412.].


Suppression of thymic lymphomas and increased nonthymic lymphomagenesis in Trp53-deficient mice lacking inducible nitric oxide synthase gene.
Trp53-deficient mice spontaneously develop lymphomas, mainly of thymic origin, although the molecular mechanism remains largely unknown. As several interaction effects between p53 and iNOS have been reported, we hypothesized that iNOS activity in the thymus is causally linked to lymphomagenesis in Trp53-deficient mice. We therefore created mouse strains with different combinations of the Trp53 and iNOS genes. Western blot and histologic analyses showed that the iNOS protein was constitutively expressed in the thymus independently of Trp53 status and its expression was enhanced in Trp53+/- and Trp53-/- mice compared to Trp53+/+ mice. Homozygous disruption of iNOS decreased the incidence of thymic lymphomas by almost 40% (p=0.087) and 90% (p<0.05) in Trp53-/- and Trp53+/- mice, respectively, compared to the respective iNOS wild-type mice but significantly (p<0.05) increased the development of nonthymic lymphomas in Trp53-/- and Trp53+/- mice. Although iNOS gene disruption did not affect the phenotype of thymic lymphomas, absence of the iNOS gene shifted the spectrum of nonthymic lymphoma from the B-cell to the T-cell lineage. RT-PCR analysis revealed enhanced expression of IL-10, which could have a promoting effect on lymphomagenesis, even without any stimulation, in the spleen of aging mice with the gene combinations Trp53-/-iNOS-/- and Trp53+/-iNOS-/- but not Trp53-/-iNOS+/+ or Trp53+/-iNOS+/+. These results suggest that iNOS could increase the development of thymic lymphomas in Trp53-deficient mice. While iNOS may have protective effects against nonthymic lymphomagenesis, the regulation of cytokine production by iNOS may be involved in the underlying mechanism of antilymphomagenesis effects in the peripheral lymphoid organ.


In situ stabilization of soil lead using phosphorus and manganese oxide: influence of plant growth.
In situ stabilization of Pb contaminated soils can be accomplished by adding P and Mn(IV) oxide. However, the long-term efficacy of in situ stabilization under continual P removal through plant growth is unknown. Moreover, the effects these treatments have on phytoavailability of other metals (Cd and Zn) commonly associated with Pb in soil are not well understood. Greenhouse experiments using sudax [Sorghum vulgare (L.) Moench] and Swiss chard [Beta vulgaris (L.) Koch] were carried out to evaluate the effects of plant growth on soil Pb bioavailability to humans after addition of P and other amendments, and the effects of these treatments on Pb, Cd, and Zn phytoavailability in three metal-contaminated soils. Eight treatments were used: zero P; 2500 mg of P as triple superphosphate (TSP); 5000 mg of P as TSP or phosphate rock (PR); 5000 mg of Mn oxide/kg; and combinations of Mn oxide and P as TSP or PR. The addition of P and/or Mn oxide significantly reduced bioavailable Pb, as measured by the physiologically based extraction test (PBET), in soils compared with the control even after extensive cropping. The PBET data also suggested that removal of P from soluble P sources by plants could negate the beneficial effects of P on bioavailable Pb, unless sufficient soluble P was added or soluble P was combined with Mn oxide. In general, Ph, Cd, and Zn concentrations in shoot tissues of sudax and Swiss chard were reduced significantly by TSP and did not change with the addition of PR. The combination of PR and Mn oxide significantly reduced Pb concentrations in plants compared with the control.


Impact of a spatial repellent on malaria incidence in two villages in Sumba, Indonesia.
A randomized, double-blinded, placebo-controlled study was conducted to examine the effect of spatial repellent (SR) in households at risk of malaria in Indonesia. Following presumptive radical cure for malaria in 180 adult men representing sentinels of new infection in four clusters within two villages, all households were given either metofluthrin or placebo mosquito coils. Weekly blood smear screening and human-landing mosquito catches were done throughout the 6 months intervention. Malaria infections occurred in 61 subjects living in placebo households and 31 subjects living in SR coil households, suggesting a 52% protective effect of SR. Likewise, anopheles indoor human landing rates were 32% lower in homes receiving SR coils. Differences in the malaria attack rate between SR- and placebo-treated homes was significant when not accounting for the effects of clustering. When the analysis was adjusted for intra-cluster correlation, the differences between SR- and placebo-treated homes were not statistically significant. The findings provide evidence of SR public health benefit and support a larger trial statistically powered to detect those effects.


Characterization of frequency-chirped dynamic nuclear polarization in rotating solids.
Continuous wave (CW) dynamic nuclear polarization (DNP) is used with magic angle spinning (MAS) to enhance the typically poor sensitivity of nuclear magnetic resonance (NMR) by orders of magnitude. In a recent publication we show that further enhancement is obtained by using a frequency-agile gyrotron to chirp incident microwave frequency through the electron resonance frequency during DNP transfer. Here we characterize the effect of chirped MAS DNP by investigating the sweep time, sweep width, center-frequency, and electron Rabi frequency of the chirps. We show the advantages of chirped DNP with a trityl-nitroxide biradical, and a lack of improvement with chirped DNP using AMUPol, a nitroxide biradical. Frequency-chirped DNP on a model system of urea in a cryoprotecting matrix yields an enhancement of 142, 21% greater than that obtained with CW DNP. We then go beyond this model system and apply chirped DNP to intact human cells. In human Jurkat cells, frequency-chirped DNP improves enhancement by 24% over CW DNP. The characterization of the chirped DNP effect reveals instrument limitations on sweep time and sweep width, promising even greater increases in sensitivity with further technology development. These improvements in gyrotron technology, frequency-agile methods, and in-cell applications are expected to play a significant role in the advancement of MAS DNP.


51 years in of Chikungunya clinical vaccine development: A historical perspective.
Chikungunya fever (CHIKF) is a mosquito-borne disease caused by Chikungunya virus (CHIKV). This virus is considered a priority pathogen to the UK government, the US National Institute of Allergy and Infectious Diseases (NIAID) and the US military personnel, due to the potential of CHIKV to cause major outbreaks. Nearly all CHIKV infections are symptomatic, often incapacitating and patients experience severe joint pain and inflammation that can last for more than one year with 0.4-0.5% fatality rates. Mother-to-child transmission has also been described. Despite this re-emerging disease has been documented in more than 100 countries in Europe, Oceania, Africa, Asia, the Caribbean, South and North America, no licensed vaccine is yet available to prevent CHIKF. Nevertheless, various developments have entered phase I and II trials and are now viable options to fight this incapacitating disease. This review focuses on the development of CHIKV vaccines that have reached the stage of clinical trials since the late 1960s up until 2018.


Distinct evolutionary trajectories of SARS-CoV-2-interacting proteins in bats and primates identify important host determinants of COVID-19.
The coronavirus disease 19 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a coronavirus that spilled over from the bat reservoir. Despite numerous clinical trials and vaccines, the burden remains immense, and the host determinants of SARS-CoV-2 susceptibility and COVID-19 severity remain largely unknown. Signatures of positive selection detected by comparative functional genetic analyses in primate and bat genomes can uncover important and specific adaptations that occurred at virus-host interfaces. We performed high-throughput evolutionary analyses of 334 SARS-CoV-2-interacting proteins to identify SARS-CoV adaptive loci and uncover functional differences between modern humans, primates, and bats. Using DGINN (Detection of Genetic INNovation), we identified 38 bat and 81 primate proteins with marks of positive selection. Seventeen genes, including the ACE2 receptor, present adaptive marks in both mammalian orders, suggesting common virus-host interfaces and past epidemics of coronaviruses shaping their genomes. Yet, 84 genes presented distinct adaptations in bats and primates. Notably, residues involved in ubiquitination and phosphorylation of the inflammatory RIPK1 have rapidly evolved in bats but not primates, suggesting different inflammation regulation versus humans. Furthermore, we discovered residues with typical virus-host arms race marks in primates, such as in the entry factor TMPRSS2 or the autophagy adaptor FYCO1, pointing to host-specific in vivo interfaces that may be drug targets. Finally, we found that FYCO1 sites under adaptation in primates are those associated with severe COVID-19, supporting their importance in pathogenesis and replication. Overall, we identified adaptations involved in SARS-CoV-2 infection in bats and primates, enlightening modern genetic determinants of virus susceptibility and severity.


Antioxidant Capacity of Selected Plant Extracts and Their Essential Oils.
The main objective of this study was the screening of some selected aromatic plants very popular in Greece, with respect to their total phenolic content, antioxidant capacity, reducing activity, and oxidative stability. All plants were extracted with the conventional method, reflux with methanol. The essential oils of the plants were also analyzed for their antioxidant properties. The total phenolic content was determined by the Folin-Ciocalteu method using gallic acid as the standard, while the phenolic substances were identified and quantified by High Performance Liquid Chromatography (HPLC) coupled with a multi-wavelength ultraviolet-visible (UV-vis) detector. The antioxidant capacity of the plant extracts was measured by their ability to scavenge free radicals such as (a) DPPH (2,2-diphenyl-1-picrylhydrazyl) and, (b) ABTS (2,2'-azinobis-(3-ethylbenzothiaziline-6- sulfonate). The Folin-Ciocalteu method proved the existence of antioxidants in the aromatic plant extracts. Taking into account the results of the DPPH and ABTS methods, the free radical scavenging capacity was confirmed. Eventually, all plants exhibited low but noticeable protection levels against lipid oxidation, as determined by the Rancimat test.


First Report of a Leaf Spot Disease of Golden Dewdrop (Duranta erecta) Caused by Pseudomonas cichorii and a Xanthomonas Species in Florida.
Duranta erecta (Verbenaceae) is used extensively in southern states as an ornamental shrub and has replaced boxwood as the most common short hedge accenting flower beds. Over the past 2 years, during warm wet periods, dark necrotic leaf spots have been observed on golden dewdrop plants in Florida. Isolations from these spots on Difco nutrient agar (NA) consistently yielded two types of bacterial colonies that were not always simultaneously present: 1) round butyrous, bright yellow and 2) flat cream-colored. Both were 2 mm in size after 48 h, gram-negative, and produced a hypersensitivity reaction (HR) on tobacco cv Hicks. Yellow colony bacteria were oxidase negative and non-fluorescent on King's medium B (KMB) (1). Cream-colored colony bacteria were oxidase positive and fluorescent on KMB. Three isolates of both types were selected for further study. Partial 16S rDNA sequencing and fatty acid analysis (FAME) MIDI Microbial Identification System (Microbial ID, Inc., Newark, DE) were used for identification of strains. The 16S rDNA primers used were; forward primer AMB14 5'-TCCAGCAATGCCGCGTGTGT-3' and reverse primer AMB13 5'-CATCCACCGCTTGTGCGGGT-3'. The PCR program consisted of an initial denaturing cycle of 95°C for 2 min followed by 30 cycles of denaturing at 95°C for 30 s, annealing at 60°C for 40 s and extension at 72°C for 1 min and one final extension at 72°C for 10 min. Using FAME analysis, the three strains of the cream-colored colony type were identified as Pseudomonas cichorii with high similarity values (0.907, 0.961, 0.819) and this corresponded well with the 16S rDNA sequences where 99% sequence identity was observed with P. cichorii strain JBC1 16S ribosomal RNA gene, partial sequence GenBank Accession No. JF951725. Two of the three yellow colony strains were identified by MIDI FAME profiles as Xanthomonas axonopodis pv. manihotis with similarity coefficients of 0.767 and 0.826. The third strain had a low similarity match to X. a. pv. carotae (0.541). The 16S rDNA sequencing of these strains showed 98% sequence identity to X. citri subsp. citri strain SA1 16S ribosomal RNA gene only, partial sequence identity JQ890091.1, thus indicating a possible undescribed X. axonopodis pathovar. To satisfy Koch's postulates, three golden dewdrop 'Golden Mound' plants were sprayed with a suspension of 108 CFU/ml of a 2-day NA culture of each strain, bagged for 24 h to raise humidity, and placed in a greenhouse. A strain of P. cichorii (P409) isolated from chrysanthemum was used as a positive control when comparing cream-colored strains. A saline buffered control was used as a negative control. Within 3 weeks, leaf spots developed on plants sprayed with each of the six strains, including positive control strain of P. cichorii. Reisolations yielded the same type of colony as the originally inoculated strain. Inoculation experiments were repeated three times with a minimum of three plants per isolate with similar results. To our knowledge, this is the first report in the United States of bacterial leaf spot caused by P. cichorii and X. axonopodis on golden dewdrop. An earlier morphological and physiological description of a Xanthomonas sp. was done on Duranta in India in 1962 (2). Due to the difficulty in controlling bacterial diseases and the popularity of Duranta spp. in the landscape, these diseases may present a problem in ornamental trade. References: (1) E. O. King et al. J. Lab. Clin. Med. 44:301, 1954. (2) M. C. Srinivasan et al. Proc. Indian Acad. Sci. 56:88, 1962.


Sub-diffusion and population dynamics of water confined in soft environments.
We have studied by using molecular dynamics computer simulations the dynamics of water confined in ionic surfactant phases, ranging from well ordered lamellar structures to micelles at low and high water loading, respectively. We have analysed in depth the main dynamical features in terms of mean-squared displacements and intermediate scattering functions, and found clear evidence of sub-diffusive behaviour. We have identified water molecules lying at the charged interface with the hydrophobic confining matrix as the main factor responsible for this unusual feature, and given a comprehensive picture of dynamics based on a very precise analysis of lifetimes at the interface. We conclude by providing, for the first time to our knowledge, a unique framework for rationalizing the existence of important dynamical heterogeneities in fluids adsorbed in soft confining environments.


Aggressive behavior during social interaction in mice is controlled by the modulation of tyrosine hydroxylase expression in the prefrontal cortex.
The Balb/c strain and the C57BL/6 strain show constitutive differences for tyrosine hydroxylase expression, and noradrenaline (NA) prefrontal transmission. Male mice of these strains also show striking differences in social interaction behaviors, with an increased aggressiveness for the Balb/c strain. To test a potential link between these neurobiological and behavioral parameters, we evaluated the behavioral effects of chronic treatment of mice with BC19, a noreburnamine compound previously known as RU24722, found to modify cell organisation, tyrosine hydoxylase (TH) expression, and its activity into the locus coeruleus (LC). We compared the pharmacological effects between the two strains in social behaviors. Our results show that the emergence of additional TH-expressing (TH+) neurons in the rostral part of the LC of Balb/c mice was associated with an increase in the density of TH+ and noradrenergic (NA+) fibers in the molecular layer in the cingular (Cg1) and prelimbic (PrL) parts of the prefrontal cortex (PFC). BC19 treatment resulted in the near-equalization of the LC number of TH+ neurons and of the density of TH+ and NA+ fibers between both strains. The aggressiveness in Balb/c mice was considerably diminished by BC19 treatment, while the originally non aggressive behavior of C57Bl/6 mice was much less affected by BC19 treatment, despite a moderate increase in some offensive behaviors. In additional control experiments, we checked the effect of BC19 on a separate test for anxiety and assessed the effect of noradrenergic N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) mediated lesions in C57BL/6 mice on social behaviors. In the present study we show that the BC19 effect in Balb/c mice was independent of anxiety as measured in the light/dark test and that DSP-4 lesions in C57BL/6 mice produced a robust increase in aggressive social interaction. Altogether, these results show that the noradrenergic system, and particularly its projections to the PFC, strongly modulates aggressive behaviors.


Liquid chromatography/mass spectrometry of malonyl-ginsenosides in the authentication of ginseng.
Different negative ion electrospray (ES) source conditions are required to concentrate the ion current in [M-H](-) for malonylated and non-malonylated ginsenosides. However, both can be ionised optimally in a single liquid chromatography/mass spectrometry (LC/MS) analysis by employing switchable voltages in the post-source ion optics of a quadrupole ion trap mass spectrometer. Coupled with automatic MS/MS scanning and post-acquisition neutral loss data analysis, this method provides a means of profiling the malonylated and acetylated ginsenosides in ginseng extracts. Analyses revealed numerous malonylated ginsenosides that could be partially characterised by serial MS/MS experiments. The ratio of mRb(1) to other isomeric forms present and to mRb(2) and mRc appears to show consistent differences among Panax ginseng (Asian ginseng), P. quinquefolius (American ginseng) and P. notoginseng (Sanchi ginseng). The ratio of malonylated to non-malonylated ginsenosides is reduced in the red form of Asian ginseng compared with the white form and there is a concomitant increase in the levels of the corresponding acetylated ginsenosides. The ability to analyse malonylated ginsenosides is an important contribution to the range of chemical characteristics that can be used to authenticate the different species of ginseng and will assist in quality control and standardisation.


Palliative care in long-term care: a system in change.
The provision of palliative care for older people within the next decade will need to be substantially different to that provided today. In long-term care settings the achievement of quality palliative care will require attention to all levels of the health and social care system, in both its formal and informal manifestations. We suggest that long-term care facilities will become the hospices of the future, caring for older people with chronic conditions with a long trajectory to death, the most common being dementia. We see this progression as inevitable and appropriate if the right support is provided. We discuss the impact that transferability and sustainability has had on the present provision of palliative care for older people and how that may affect the future. Four forces which are important factors in public policy; leadership, a culture that supports learning throughout the care process, an emphasis on effective team development and the use of information technologies for quality activities are used as a framework for our vision of social planning. We then go on to discuss the impact of costs, workforce, service planning and public awareness as vital areas where progress needs to be carefully tackled. We suggest some likely poor outcomes if this planning does not occur, but indicate that if planning and implementation is effective then services can provide the kind of care the baby boomer generation seeks.


A label-free, electrochemical SERS-based assay for detection of DNA hybridization and discrimination of mutations.
A label-free, surface-enhanced Raman spectroscopy-based assay for detecting DNA hybridization at an electrode surface and for distinguishing between mutations in DNA is demonstrated. Surface-immobilized DNA is exposed to a binding agent that is selective for dsDNA and acts as a reporter molecule. Upon application of a negative potential, the dsDNA denatures into its constituent strands, and the changes in the spectra of the reporter molecule are monitored. This method has been used to distinguish between a wild-type, 1653C/T single-point mutation and ΔF508 triplet deletion in the CFTR gene. The use of dsDNA-selective binding agents as reporter molecules in a discrimination assay removes the burden of synthetically modifying the target to be detected, while retaining flexibility in the choice of the reporter molecule.


Glycyrrhizin inhibits influenza A virus uptake into the cell.
We investigated the mechanism by which glycyrrhizin (GL), the main active component of licorice roots, protects cells from infection with influenza A virus (IAV). We found that GL treatment leads to a clear reduction in the number of IAV-infected human lung cells as well as a reduction in the CCID50 titer by 90%. The antiviral effect, however, was limited to one or two virus replication cycles. Analysis of different GL treatment protocols suggested that the antiviral effect of GL was limited to an early step in the virus replication cycle. A direct inhibitory action of GL on IAV particles could be excluded and GL did not interact with virus receptor binding either. The antiviral effect of GL was abolished by treatment 1h after virus infection, whereas pre-treatment and treatment during and after virus adsorption led to a reduction in the cytopathic effect, reduced viral RNA within the cells and in the cell supernatants, and reduced viral hemagglutination titers. Detailed virus uptake analyses unambiguously demonstrated reduced virus uptake in various GL-treated cells. These observations lead to the conclusion, that the antiviral activity of GL is mediated by an interaction with the cell membrane which most likely results in reduced endocytotic activity and hence reduced virus uptake. These insights might help in the design of structurally related compounds leading to potent anti-influenza therapeutics.


Normobaric hyperoxia markedly reduces brain damage and sensorimotor deficits following brief focal ischaemia.
'True' transient ischaemic attacks are characterized not only clinically, but also radiologically by a lack of corresponding changes on magnetic resonance imaging. During a transient ischaemic attack it is assumed that the affected tissue is penumbral but rescued by early spontaneous reperfusion. There is, however, evidence from rodent studies that even brief focal ischaemia not resulting in tissue infarction can cause extensive selective neuronal loss associated with long-lasting sensorimotor impairment but normal magnetic resonance imaging. Selective neuronal loss might therefore contribute to the increasingly recognized cognitive impairment occurring in patients with transient ischaemic attacks. It is therefore relevant to consider treatments to reduce brain damage occurring with transient ischaemic attacks. As penumbral neurons are threatened by markedly constrained oxygen delivery, improving the latter by increasing arterial O2 content would seem logical. Despite only small increases in arterial O2 content, normobaric oxygen therapy experimentally induces significant increases in penumbral O2 pressure and by such may maintain the penumbra alive until reperfusion. Nevertheless, the effects of normobaric oxygen therapy on infarct volume in rodent models have been conflicting, although duration of occlusion appeared an important factor. Likewise, in the single randomized trial published to date, early-administered normobaric oxygen therapy had no significant effect on clinical outcome despite reduced diffusion-weighted imaging lesion growth during therapy. Here we tested the hypothesis that normobaric oxygen therapy prevents both selective neuronal loss and sensorimotor deficits in a rodent model mimicking true transient ischaemic attack. Normobaric oxygen therapy was applied from the onset and until completion of 15 min distal middle cerebral artery occlusion in spontaneously hypertensive rats, a strain representative of the transient ischaemic attack-prone population. Whereas normoxic controls showed normal magnetic resonance imaging but extensive cortical selective neuronal loss associated with microglial activation (present both at Day 14 in vivo and at Day 28 post-mortem) and marked and long-lasting sensorimotor deficits, normobaric oxygen therapy completely prevented sensorimotor deficit (P < 0.02) and near-completely Day 28 selective neuronal loss (P < 0.005). Microglial activation was substantially reduced at Day 14 and completely prevented at Day 28 (P = 0.002). Our findings document that normobaric oxygen therapy administered during ischaemia nearly completely prevents the neuronal death, microglial inflammation and sensorimotor impairment that characterize this rodent true transient ischaemic attack model. Taken together with the available literature, normobaric oxygen therapy appears a promising therapy for short-lasting ischaemia, and is attractive clinically as it could be started at home in at-risk patients or in the ambulance in subjects suspected of transient ischaemic attack/early stroke. It may also be a straightforward adjunct to reperfusion therapies, and help prevent subtle brain damage potentially contributing to long-term cognitive and sensorimotor impairment in at-risk populations.


Ammonite habitat revealed via isotopic composition and comparisons with co-occurring benthic and planktonic organisms.
Ammonites are among the best-known fossils of the Phanerozoic, yet their habitat is poorly understood. Three common ammonite families (Baculitidae, Scaphitidae, and Sphenodiscidae) co-occur with well-preserved planktonic and benthic organisms at the type locality of the upper Maastrichtian Owl Creek Formation, offering an excellent opportunity to constrain their depth habitats through isotopic comparisons among taxa. Based on sedimentary evidence and the micro- and macrofauna at this site, we infer that the 9-m-thick sequence was deposited at a paleodepth of 70-150 m. Taxa present throughout the sequence include a diverse assemblage of ammonites, bivalves, and gastropods, abundant benthic foraminifera, and rare planktonic foraminifera. No stratigraphic trends are observed in the isotopic data of any taxon, and thus all of the data from each taxon are considered as replicates. Oxygen isotope-based temperature estimates from the baculites and scaphites overlap with those of the benthos and are distinct from those of the plankton. In contrast, sphenodiscid temperature estimates span a range that includes estimates of the planktonic foraminifera and of the warmer half of the benthic values. These results suggest baculites and scaphites lived close to the seafloor, whereas sphenodiscids sometimes inhabited the upper water column and/or lived closer to shore. In fact, the rarity and poorer preservation of the sphenodiscids relative to the baculites and scaphites suggests that the sphenodiscid shells may have only reached the Owl Creek locality by drifting seaward after death.


Rab1a regulates sorting of early endocytic vesicles.
We previously reported that Rab1a is associated with asialoorosomucoid (ASOR)-containing early endocytic vesicles, where it is required for their microtubule-based motility. In Rab1a knockdown (KD) cell lines, ASOR failed to segregate from its receptor and, consequently, did not reach lysosomes for degradation, indicating a defect in early endosome sorting. Although Rab1 is required for Golgi/endoplasmic reticulum trafficking, this process was unaffected, likely due to retained expression of Rab1b in these cells. The present study shows that Rab1a has a more general role in endocytic vesicle processing that extends to EGF and transferrin (Tfn) trafficking. Compared with results in control Huh7 cells, EGF accumulated in aggregates within Rab1a KD cells, failing to reach lysosomal compartments. Tfn, a prototypical example of recycling cargo, accumulated in a Rab11-mediated slow-recycling compartment in Rab1a KD cells, in contrast to control cells, which sort Tfn into a fast-recycling Rab4 compartment. These data indicate that Rab1a is an important regulator of early endosome sorting for multiple cargo species. The effectors and accessory proteins recruited by Rab1a to early endocytic vesicles include the minus-end-directed kinesin motor KifC1, while others remain to be discovered.


How genomic selection has increased rates of genetic gain and inbreeding in the Australian national herd, genomic information nucleus, and bulls.
Genomic selection has been commonly used for selection for over a decade. In this time, the rate of genetic gain has more than doubled in some countries, while inbreeding per year has also increased. Inbreeding can result in a loss of genetic diversity, decreased long-term response to selection, reduced animal performance and ultimately, decreased farm profitability. We quantified and compared changes in genetic gain and diversity resulting from genomic selection in Australian Holstein and Jersey cattle populations. To increase the accuracy of genomic selection, Australia has had a female genomic reference population since 2013, specifically designed to be representative of commercial populations and thus including both Holstein and Jersey cows. Herds that kept excellent health and fertility data were invited to join this population and most their animals were genotyped. In both breeds, the rate of genetic gain and inbreeding was greatest in bulls, and then the female genomic reference population, and finally the wider national herd. When comparing pre- and postgenomic selection, the rates of genetic gain for the national economic index has increased by ~160% in Holstein females and ~100% in Jersey females. This has been accompanied by doubling of the rates of inbreeding in female populations, and the rate of inbreeding has increased several fold in Holstein bulls since the widespread use of genomic selection. Where cow genotype data were available to perform a more accurate genomic analysis, greater rates of pedigree and genomic inbreeding were observed, indicating actual inbreeding levels could be underestimated in the national population due to gaps in pedigrees. Based on current rates of genetic gain, the female reference population is progressing ahead of the national herd and could be used to infer and track the future inbreeding and genetic trends of the national herds.


Assessment of cardiac sympathetic regulation by respiratory-related arterial pressure variability in the rat.
1. Mechanical ventilation evokes a corresponding arterial pressure variability (APV) which is decreased by beta-adrenoceptor antagonism. Therefore, in this study we set out to determine whether the respiratory-related APV can be used to assess cardiac sympathetic tone. 2. Computer-generated broad-band mechanical ventilation (0-3 Hz) was applied to Sprague-Dawley rats that had been anaesthetized with ketamine and paralysed with pancuronium. APV and its relationship to lung volume variability (LVV-APV) was systematically quantified with auto- or cross-spectral frequency domain analysis. 3. APV and LVV-APV transfer magnitudes between 0.5 and 1.5 Hz showed dose-dependent suppression by propranolol from 0.01 to 1 mg kg-1, while the static value of arterial pressure remained unchanged. Stroke volume variability, assessed by the use of a pulse contour method, exhibited a similar pattern of suppression by propranolol. In contrast, heart rate variability was not lowered with propranolol. 4. The effect of propranolol on respiratory-related APV persisted even in the presence of combined alpha-adrenoceptor and muscarinic receptor blockade by phentolamine and atropine. 5. The frequency range of 0.5-1.0 Hz was optimal for LVV-APV transfer magnitude to correlate with cardiac sympathetic tone. 6. We conclude that respiratory-related APV may provide a valid assessment of cardiac sympathetic regulation which is independent of parasympathetic and vascular sympathetic influences in ketamine-anaesthetized and positive pressure-ventilated rats.


Evidence from knockout mice for distinct implications of neuropeptide-Y Y2 and Y4 receptors in the circadian control of locomotion, exploration, water and food intake.
Members of the neuropeptide-Y (NPY) family acting via Y2 and/or Y4 receptors have been proposed to participate in the control of ingestive behaviour and energy homeostasis. Since these processes vary between day and night, we explored the circadian patterns of locomotor, exploratory and ingestive behaviour in mice with disrupted genes for Y2 (Y2-/-) or Y4 (Y4-/-) receptors. To this end, the LabMaster system was used and its utility for the analysis of changes in circadian activity and ingestion caused by gene knockout evaluated. Female animals, aged 27weeks on average, were housed singly in cages fitted with sensors for water and food intake and two infrared frames for recording ambulation and rearing under a 12h light/dark cycle for 4days. Relative to WT animals, diurnal locomotion, exploration, drinking and feeding were reduced, whereas nocturnal locomotion was enhanced in Y2-/- mice. In contrast, Y4-/- mice moved more but ate and drank less during the photophase, while they ate more and explored less during the scotophase. Both Y2-/- and Y4-/- mice weighed more than WT mice. These findings attest to a differential role of Y2 and Y4 receptor signalling in the circadian control of behaviours that balance energy intake and energy expenditure. These phenotypic traits can be sensitively and continuously recorded by the LabMaster system.


Featured Article: microRNA-125a in pulmonary hypertension: Regulator of a proliferative phenotype of endothelial cells.
Vascular remodeling due to excessive proliferation of endothelial and smooth muscle cells is a hallmark feature of pulmonary hypertension. microRNAs (miRNAs) are a class of small, non-coding RNA fragments that have recently been associated with remodeling of pulmonary arteries, in particular by silencing the bone morphogenetic protein receptor type II (BMPR2). Here we identified a novel pathway involving the concerted action of miR-125a, BMPR2 and cyclin-dependent kinase inhibitors (CDKN) that controls a proliferative phenotype of endothelial cells. An in silico approach predicted miR-125a to target BMPR2. Functional inhibition of miR-125a resulted in increased proliferation of these cells, an effect that was found accompanied by upregulation of BMPR2 and reduced expression of the tumor suppressors CDKN1A (p21) and CDKN2A (p16). These data were confirmed in experimental pulmonary hypertension in vivo. Levels of miR-125a were elevated in lung tissue of hypoxic animals that develop pulmonary hypertension. In contrast, circulating levels of miR-125a were found to be lower in mice with pulmonary hypertension as compared to control mice. Similar findings were observed in a small cohort of patients with precapillary pulmonary hypertension. These translational data emphasize the pathogenetic role of miR-125a in pulmonary vascular remodeling.


Polyfunctional CD4(+) and CD8(+) T cell responses to tuberculosis antigens in HIV-1-infected patients before and after anti-retroviral treatment.
Tuberculosis (TB) kills 2 million people per year and infection with HIV is the most potent known risk factor for progression to active TB. An understanding of the immune response to TB Ags in HIV-infected patients is required to develop optimal TB vaccines and diagnostics. We assessed polyfunctional (IFN-gamma(+)IL-2(+)TNF-alpha(+)) T cell responses to TB Ags in three groups of HIV-1-infected patients dependent on their TB status, CD4 counts, and anti-retroviral exposure. We found that although the proportion of IFN-gamma cells in response to TB Ags was higher in patients with low CD4 counts, the responding cells changed from a polyfunctional CD4(+) to a monofunctional CD8(+) response. The overall polyfunctionality of the cells was restored by 12 mo of anti-retroviral therapy and primarily involved CD4(+) T cells with an effector memory phenotype. These findings have major implications for diagnosis of TB and in vaccine development strategies for TB in HIV-1-infected patients.


Adaptation of the black yeast Wangiella dermatitidis to ionizing radiation: molecular and cellular mechanisms.
Observations of enhanced growth of melanized fungi under low-dose ionizing radiation in the laboratory and in the damaged Chernobyl nuclear reactor suggest they have adapted the ability to survive or even benefit from exposure to ionizing radiation. However, the cellular and molecular mechanism of fungal responses to such radiation remains poorly understood. Using the black yeast Wangiella dermatitidis as a model, we confirmed that ionizing radiation enhanced cell growth by increasing cell division and cell size. Using RNA-seq technology, we compared the transcriptomic profiles of the wild type and the melanin-deficient wdpks1 mutant under irradiation and non-irradiation conditions. It was found that more than 3000 genes were differentially expressed when these two strains were constantly exposed to a low dose of ionizing radiation and that half were regulated at least two fold in either direction. Functional analysis indicated that many genes for amino acid and carbohydrate metabolism and cell cycle progression were down-regulated and that a number of antioxidant genes and genes affecting membrane fluidity were up-regulated in both irradiated strains. However, the expression of ribosomal biogenesis genes was significantly up-regulated in the irradiated wild-type strain but not in the irradiated wdpks1 mutant, implying that melanin might help to contribute radiation energy for protein translation. Furthermore, we demonstrated that long-term exposure to low doses of radiation significantly increased survivability of both the wild-type and the wdpks1 mutant, which was correlated with reduced levels of reactive oxygen species (ROS), increased production of carotenoid and induced expression of genes encoding translesion DNA synthesis. Our results represent the first functional genomic study of how melanized fungal cells respond to low dose ionizing radiation and provide clues for the identification of biological processes, molecular pathways and individual genes regulated by radiation.


What is social about social perception research?
A growing consensus in social cognitive neuroscience holds that large portions of the primate visual brain are dedicated to the processing of social information, i.e., to those aspects of stimuli that are usually encountered in social interactions such as others' facial expressions, actions, and symbols. Yet, studies of social perception have mostly employed simple pictorial representations of conspecifics. These stimuli are social only in the restricted sense that they physically resemble objects with which the observer would typically interact. In an equally important sense, however, these stimuli might be regarded as "non-social": the observer knows that they are viewing pictures and might therefore not attribute current mental states to the stimuli or might do so in a qualitatively different way than in a real social interaction. Recent studies have demonstrated the importance of such higher-order conceptualization of the stimulus for social perceptual processing. Here, we assess the similarity between the various types of stimuli used in the laboratory and object classes encountered in real social interactions. We distinguish two different levels at which experimental stimuli can match social stimuli as encountered in everyday social settings: (1) the extent to which a stimulus' physical properties resemble those typically encountered in social interactions and (2) the higher-level conceptualization of the stimulus as indicating another person's mental states. We illustrate the significance of this distinction for social perception research and report new empirical evidence further highlighting the importance of mental state attribution for perceptual processing. Finally, we discuss the potential of this approach to inform studies of clinical conditions such as autism.


Anisotropic Superfluid Behavior of a Dipolar Bose-Einstein Condensate.
We present transport measurements on a dipolar superfluid using a Bose-Einstein condensate of ^{162}Dy with strong magnetic dipole-dipole interactions. By moving an attractive laser beam through the condensate we observe an anisotropy in superfluid flow. This observation is compatible with an anisotropic critical velocity for the breakdown of dissipationless flow, which, in the spirit of the Landau criterion, can directly be connected to the anisotropy of the underlying dipolar excitation spectrum. In addition, the heating rate above this critical velocity reflects the same anisotropy. Our observations are in excellent agreement with simulations based on the Gross-Pitaevskii equation and highlight the effect of dipolar interactions on macroscopic transport properties, rendering dissipation anisotropic.


Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway.
The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes (PSs), excludes the PS maturation mediator Rab7, and triggers binding of exocytosis mediators Rab11 and Sec15. This reprogramming redirects PSs to the non-degradative pathway, allowing A. fumigatus to escape cells by outgrowth and expulsion as well as transfer of conidia between cells. The clinical relevance is supported by the identification of a single nucleotide polymorphism in the non-coding region of the S100A10 (p11) gene that affects mRNA and protein expression in response to A. fumigatus and is associated with protection against invasive pulmonary aspergillosis. These findings reveal the role of p11 in mediating fungal PS evasion.


Maternal melatonin: Effective intervention against developmental programming of cardiovascular dysfunction in adult offspring of complicated pregnancy.
Adopting an integrative approach, by combining studies of cardiovascular function with those at cellular and molecular levels, this study investigated whether maternal treatment with melatonin protects against programmed cardiovascular dysfunction in the offspring using an established rodent model of hypoxic pregnancy. Wistar rats were divided into normoxic (N) or hypoxic (H, 10% O2 ) pregnancy ± melatonin (M) treatment (5 μg·ml-1 .day-1 ) in the maternal drinking water. Hypoxia ± melatonin treatment was from day 15-20 of gestation (term is ca. 22 days). To control for possible effects of maternal hypoxia-induced reductions in maternal food intake, additional dams underwent pregnancy under normoxic conditions but were pair-fed (PF) to the daily amount consumed by hypoxic dams from day 15 of gestation. In one cohort of animals from each experimental group (N, NM, H, HM, PF, PFM), measurements were made at the end of gestation. In another, following delivery of the offspring, investigations were made at adulthood. In both fetal and adult offspring, fixed aorta and hearts were studied stereologically and frozen hearts were processed for molecular studies. In adult offspring, mesenteric vessels were isolated and vascular reactivity determined by in-vitro wire myography. Melatonin treatment during normoxic, hypoxic or pair-fed pregnancy elevated circulating plasma melatonin in the pregnant dam and fetus. Relative to normoxic pregnancy, hypoxic pregnancy increased fetal haematocrit, promoted asymmetric fetal growth restriction and resulted in accelerated postnatal catch-up growth. Whilst fetal offspring of hypoxic pregnancy showed aortic wall thickening, adult offspring of hypoxic pregnancy showed dilated cardiomyopathy. Similarly, whilst cardiac protein expression of eNOS was downregulated in the fetal heart, eNOS protein expression was elevated in the heart of adult offspring of hypoxic pregnancy. Adult offspring of hypoxic pregnancy further showed enhanced mesenteric vasoconstrictor reactivity to phenylephrine and the thromboxane mimetic U46619. The effects of hypoxic pregnancy on cardiovascular remodelling and function in the fetal and adult offspring were independent of hypoxia-induced reductions in maternal food intake. Conversely, the effects of hypoxic pregnancy on fetal and postanal growth were similar in pair-fed pregnancies. Whilst maternal treatment of normoxic or pair-fed pregnancies with melatonin on the offspring cardiovascular system was unremarkable, treatment of hypoxic pregnancies with melatonin in doses lower than those recommended for overcoming jet lag in humans enhanced fetal cardiac eNOS expression and prevented all alterations in cardiovascular structure and function in fetal and adult offspring. Therefore, the data support that melatonin is a potential therapeutic target for clinical intervention against developmental origins of cardiovascular dysfunction in pregnancy complicated by chronic fetal hypoxia.


Hot topics in parenteral nutrition. Rationale for using new lipid emulsions in parenteral nutrition and a review of the trials performed in adults.
Lipids traditionally used in parenteral nutrition are based on n-6 fatty acid-rich vegetable oils such as soyabean oil. This practice may not be optimal because it may present an excessive supply of linoleic acid. Alternatives to the use of soyabean oil include its partial replacement by so-called medium-chain TAG (MCT), olive oil or fish oil, either alone or in combination. Lipid emulsions containing MCT are well established, but those containing olive oil and fish oil, although commercially available, are still undergoing trials in different patient groups. Emulsions containing olive oil or fish oil are well tolerated and without adverse effects in a wide range of adult patients. An olive oil-soyabean oil emulsion has been used in quite small studies in critically-ill patients and in patients with trauma or burns with little real evidence of advantage over soyabean oil or MCT-soyabean oil. Fish oil-containing lipid emulsions have been used in adult patients post surgery (mainly gastrointestinal). This approach has been associated with alterations in patterns of inflammatory mediators and in immune function and, in some studies, a reduction in the length of stay in the intensive care unit and in hospital. One study indicates that peri-operative administration of fish oil may be superior to post-operative administration. Fish oil has been used in critically-ill adults. Here, the influence on inflammatory processes, immune function and clinical end points is not clear, since there are too few studies and those that are available report contradictory findings. One important factor is the dose of fish oil required to influence clinical outcomes. Further studies that are properly designed and adequately powered are required in order to strengthen the evidence base relating to the use of lipid emulsions that include olive oil and fish oil in critically-ill patients and in patients post surgery.


The galactic center: is it a massive black hole?
Studies of active galactic nuclei constitute one of the major efforts in astronomy. Massive black holes are the most likely source for the enormous energy radiated from such nuclei. Observations reviewed here suggest unusual activity and the possible existence of a massive black hole in the nucleus of our galaxy. Because of its proximity to Earth, our galactic nucleus can be observed in unsurpassed detail and may serve as the Rosetta stone both for deciphering active galactic nuclei and for confirming the existence of a massive black hole.