Contrast agents for photoacoustic imaging: a review of stem cell tracking.
With the advent of stem cell therapy for spinal cord injuries, stroke, burns, macular degeneration, heart diseases, diabetes, rheumatoid arthritis and osteoarthritis; the need to track the survival, migration pathways, spatial destination and differentiation of transplanted stem cells in a clinical setting has gained increased relevance. Indeed, getting regulatory approval to use these therapies in the clinic depends on biodistribution studies. Although optoacoustic imaging (OAI) or photoacoustic imaging can detect functional information of cell activities in real-time, the selection and application of suitable contrast agents is essential to achieve optimal sensitivity and contrast for sensing at clinically relevant depths and can even provide information about molecular activity. This review explores OAI methodologies in conjunction with the specific application of exogenous contrast agents in comparison to other imaging modalities and describes the properties of exogenous contrast agents for quantitative and qualitative monitoring of stem cells. Specific characteristics such as biocompatibility, the absorption coefficient, and surface functionalization are compared and how the labelling efficiency translates to both short and long-term visualization of mesenchymal stem cells is explored. An overview of novel properties of recently developed optoacoustic contrast agents and their capability to detect disease and recovery progression in clinical settings is provided which includes newly developed exogenous contrast agents to monitor stem cells in real-time for multimodal sensing.


A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease.
Dysregulation of several metabolite pathways, including branched-chain amino acids (BCAAs), are associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and insulin resistance in adults, while studies in youth reported conflicting results. We explored whether, independently of obesity and insulin resistance, obese adolescents with NAFLD display a metabolomic signature consistent with disturbances in amino acid and lipid metabolism. A total of 180 plasma metabolites were measured by a targeted metabolomic approach in 78 obese adolescents with (n = 30) or without (n = 48) NAFLD assessed by magnetic resonance imaging (MRI). All subjects underwent an oral glucose tolerance test and subsets of patients underwent a two-step hyperinsulinemic-euglycemic clamp and/or a second MRI after a 2.2 ± 0.8-year follow-up. Adolescents with NAFLD had higher plasma levels of valine (p = 0.02), isoleucine (p = 0.03), tryptophan (p = 0.02), and lysine (p = 0.02) after adjustment for confounding factors. Circulating BCAAs were negatively correlated with peripheral and hepatic insulin sensitivity. Furthermore, higher baseline valine levels predicted an increase in hepatic fat content (HFF) at follow-up (p = 0.01). These results indicate that a dysregulation of BCAA metabolism characterizes obese adolescents with NAFLD independently of obesity and insulin resistance and predict an increase in hepatic fat content over time.


Compartmentalization and Unidirectional Cross-Domain Molecule Shuttling of Organometallic Single-Chain Nanoparticles.
Compartmentalization and unidirectional cross-domain molecule shuttling are omnipresent in proteins, and play key roles in molecular recognition, enzymatic reaction, and other living functions. Nanomachinery design emulating these biological functions is being considered as one of the most ambitious and challenging tasks in modern chemistry and nanoscience. Here, we present a biomimetic nanomachinery design using single-chain technology. Stepwise complex of the outer blocks of water-soluble linear ABC triblock terpolymer to copper ions yields dumbbell-shaped single-chain nanoparticle. A novel nanomachine capable of compartmentalization and unidirectional cross-domain molecule shuttling has been achieved upon ascorbic acid reduction, leading to synergistically donating/accepting copper centers between discrete double heads, overall dumbbell-to-tadpole configurational transition, and intake of oxidized ascorbic acid into reconstructed head. Subsequent air oxidation results in the inverse molecule shuttling and configurational transition processes. This is the first demonstration of biomimetic nanomachinery design that is capable of compartmentalization and unidirectional cross-domain molecule shuttling, exemplified simply using a new single-chain technology.


An Official American Thoracic Society Research Statement: Implementation Science in Pulmonary, Critical Care, and Sleep Medicine.
Many advances in health care fail to reach patients. Implementation science is the study of novel approaches to mitigate this evidence-to-practice gap. The American Thoracic Society (ATS) created a multidisciplinary ad hoc committee to develop a research statement on implementation science in pulmonary, critical care, and sleep medicine. The committee used an iterative consensus process to define implementation science and review the use of conceptual frameworks to guide implementation science for the pulmonary, critical care, and sleep community and to explore how professional medical societies such as the ATS can promote implementation science. The committee defined implementation science as the study of the mechanisms by which effective health care interventions are either adopted or not adopted in clinical and community settings. The committee also distinguished implementation science from the act of implementation. Ideally, implementation science should include early and continuous stakeholder involvement and the use of conceptual frameworks (i.e., models to systematize the conduct of studies and standardize the communication of findings). Multiple conceptual frameworks are available, and we suggest the selection of one or more frameworks on the basis of the specific research question and setting. Professional medical societies such as the ATS can have an important role in promoting implementation science. Recommendations for professional societies to consider include: unifying implementation science activities through a single organizational structure, linking front-line clinicians with implementation scientists, seeking collaborations to prioritize and conduct implementation science studies, supporting implementation science projects through funding opportunities, working with research funding bodies to set the research agenda in the field, collaborating with external bodies responsible for health care delivery, disseminating results of implementation science through scientific journals and conferences, and teaching the next generation about implementation science through courses and other media. Implementation science plays an increasingly important role in health care. Through support of implementation science, the ATS and other professional medical societies can work with other stakeholders to lead this effort.


A simple approach for the development of urban climatic maps based on the urban characteristics in Tainan, Taiwan.
Motivated by the increasing thermal load in urban environment, this work established Urban Climatic map (UCmap) focusing on thermal environment issues based on urban development factors, e.g., land cover and building characteristics, representing thermal load of human body and ventilation path in the urban structures. In the established process of UCmap in this work, Tainan city, which is a highly developed city in southern Taiwan, is selected as the research area. A 50-m resolution grid is used to capture urban development factors and the climate data based on 1 year of mobile and fix-point measurements, from which the thermal load and the wind environment map are constructed. The results herein reveal that a higher urban development level is associated with a higher thermal load, and similar areas are more likely than others to suffer from an extreme thermal load and low wind pass conditions. Open and sparse low-rise buildings constitute the most appropriate urban characteristics for urban built environment in Tainan. By the simple approach of establishing UCmap, the microclimate condition and development intensity of regions can be easily detected and linked, for example the compact high-rise areas should be limited by floor area ratio in order to prevent the formation of hot spots. The government, urban planners, and architects without a meteorological background can efficiently obtain climate information by way of mapping the certain area, and making regulations to mitigate the growing problem of thermal stress and urban heat island.


An inclusive, real-world investigation of persuasion in language and verbal behavior.
Linguistic features of a message necessarily shape its persuasive appeal. However, studies have largely examined the effect of linguistic features on persuasion in isolation and do not incorporate properties of language that are often involved in real-world persuasion. As such, little is known about the key verbal dimensions of persuasion or the relative impact of linguistic features on a message's persuasive appeal in real-world social interactions. We collected large-scale data of online social interactions from a social media website in which users engage in debates in an attempt to change each other's views on any topic. Messages that successfully changed a user's views are explicitly marked by the user themselves. We simultaneously examined linguistic features that have been previously linked with message persuasiveness between persuasive and non-persuasive messages. Linguistic features that drive persuasion fell along three central dimensions: structural complexity, negative emotionality, and positive emotionality. Word count, lexical diversity, reading difficulty, analytical language, and self-references emerged as most essential to a message's persuasive appeal: messages that were longer, more analytic, less anecdotal, more difficult to read, and less lexically varied had significantly greater odds of being persuasive. These results provide a more parsimonious understanding of the social psychological pathways to persuasion as it operates in the real world through verbal behavior. Our results inform theories that address the role of language in persuasion, and provide insight into effective persuasion in digital environments.


Implementing Electronic Patient-Reported Outcome Measures in Outpatient Cosmetic Surgery Clinics: An Exploratory Qualitative Study.
Patient-reported outcome measure (PROM) data are increasingly being collected over the internet or on a smart device by means of electronic versions (e-PROMs). Limited evidence exists about factors influencing e-PROM implementation in outpatient clinics. The authors sought to identify barriers to collection of PRO data from different locations (home or cosmetic surgery office) by means of different modes (paper vs e-PROM) from the perspective of patients, plastic surgeons, and clinic administrative staff; and to explore patient preferences for the design of e-PROM platforms. Semistructured interviews were conducted with 11 patients, 3 cosmetic surgeons, and administrative staff. Patients were shown 1 of the 3 PROMs (ie, the BODY-Q Satisfaction with Body scale, BREAST-Q Augmentation Module Satisfaction with Breast scale, or FACE-Q Satisfaction with Facial Appearance scale). The formats included paper and electronic (REDCap and TickiT) on a tablet and laptop computer. The interviews were audio-recorded and transcribed verbatim. Qualitative descriptive analysis was conducted. Patients and providers preferred electronic over paper format. The flexibility of the hardware, data entry point (remote location vs point-of-care), and the privacy of the data were the most recurring themes from the patient's perspective. The objective of collecting PROM data, role in peer-benchmarking, and return on investment were key to surgeons and administrative staff. The e-PROMs were well accepted in the community setting by the patients and plastic surgeons alike. The design and interface features of e-PROMs were explored in this study, which may be useful for future, mixed method studies evaluating the implementation of e-PROMs.


Structural determinants of affinity for the phencyclidine binding site of the N-methyl-D-aspartate receptor complex: discovery of a rigid phencyclidine analogue of high binding affinity.
To learn more about the binding conformation of phencyclidine (PCP) and to arrive at analogues of higher affinity, which may serve as noncompetitive N-methyl-D-aspartate receptor antagonists, eight optically pure PCP analogues were designed with the aid of computer. These compounds represent conformationally constrained versions of PCP in which the motion of the phenyl ring is frozen, thus allowing a determination of the orientation of the phenyl ring relevant to binding. The analogues were synthesized by a Diels-Alder strategy and tested in a radioligand binding assay to evaluate their affinity for the PCP binding site of the N-methyl-D-aspartate receptor complex. One of the analogues was found to bind with nanomolar affinity (IC50 = 19 nM) and to be 73-fold more potent in binding than its enantiomer. These results, which further elucidate the structural determinants of high affinity binding, should aid both in the design of higher affinity molecular probes of the PCP binding site and in the discovery of potential neuroprotective agents.


Experimental evidence from active placement efforts among unemployed in Sweden.
This article uses data from a field experiment in Sweden to analyze the effects of active placement efforts. In particular, the relative efficiency between combining job-search monitoring and job-search assistance, and monitoring alone, is analyzed. Although the impact estimates are generally imprecisely estimated, a general conclusion is that placement programs are effective policies in increasing the job exit rate for various groups of unemployed. I find that monitoring of job search is an efficient method to increase off-unemployment exit rate both alone and combined with job-search assistance services. The results, however, indicate that the combined services generate more permanent job exits.


Cellular adhesion mediated by factor J, a complement inhibitor. Evidence for nucleolin involvement.
Factor J (FJ) is a complement inhibitor that acts on the classical and the alternative pathways. We demonstrated FJ-cell interactions in fluid phase by flow cytometry experiments using the cell lines Jurkat, K562, JY, and peripheral blood lymphocytes. FJ bound to plastic plates was able to induce in vitro adhesion of these cells with potency equivalent to fibronectin. As evidence for the specificity of this reaction, the adhesion was blocked by MAJ2, an anti-FJ monoclonal antibody, and by soluble FJ. Attachment of the cells required active metabolism and cytoskeletal integrity. The glycosaminoglycans heparin, heparan sulfate, or chondroitin sulfates A, B, and C inhibited to varying degrees the binding of FJ to cells, as did treatment with chondroitinase ABC. In the search for a putative receptor, a protein of 110 kDa was isolated by affinity chromatography, and microsequence analysis identified this protein as nucleolin. Confocal microscopy evidenced the presence of nucleolin in cell membrane by immunofluorescence with monoclonal (D3) and polyclonal anti-nucleolin antibodies in Jurkat cells. The interaction FJ-nucleolin was evidenced by Western blot and enzyme-linked immunosorbent assay. Furthermore, purified nucleolin and D3 inhibited adhesion of Jurkat cells to immobilized FJ, suggesting that the interaction was specific and that nucleolin mediated the binding.


The prevalence and correlates of the double burden of malnutrition among women in Ghana.
Anaemia and underweight or overweight/obesity are major public health problems driving maternal and child mortality in low- and middle-income countries. While the burden of these conditions is recognised, the evidence for the co-occurrence of these conditions is fragmented and mixed, especially at the individual level. Further, many studies have focused on families and communities. The different pathways for the occurrence of anaemia and BMI challenges indicate that an individual can potentially live with both conditions and suffer the complications. This study examined the prevalence and factors associated with the co-occurrence of anaemia and BMI challenges among a cohort of women in Ghana. Data from the 2014 Ghana Demographic and Health Survey were used. The sample size was 4 337 women aged 15-49 years who were not pregnant during the survey. Women who suffered simultaneously from underweight or overweight/obesity and anaemia were considered as having the double burden of malnutrition. The data were analysed using descriptive statistics, Chi-square test and logistic regression in STATA. One-fifth of the participants were overweight (21%), 4% were underweight and about one-tenth were obese (12%). The prevalence of anaemia was 41%. Only one in three women had normal weight and was not anaemic (34%). About 14% of the women experienced the double burden of malnutrition. Being overweight and anaemic (57%) was the most common form of this double burden. Age, marital status, parity, and wealth were t key risk factors associated with the double burden of malnutrition. The findings from this study show that women experience multiple nutritional challenges concurrently and that only a few women had healthy nutritional status. This information is particularly important and can be introduced into health education programmes to help address misconceptions about body weight and health.


Evaluation of temperature gradient gel electrophoresis for the analysis of prey DNA within the guts of invertebrate predators.
The utility of temperature gradient gel electrophoresis (TGGE) as a means of analysing the gut contents of predators was evaluated. Generalist predators consume multiple prey species and a species-specific primer approach may not always be a practical means of analysing predator responses to prey diversity in complex and biodiverse ecosystems. General invertebrate primers were used to amplify the gut contents of predators, generating banding patterns that identified component prey remains. There was no evidence of dominance of the polymerase chain reaction (PCR) by predator DNA. When applied to field samples of the carabid predator Pterostichus melanarius (Illiger) nine banding patterns were detected, including one for aphids. To further distinguish between species, group-specific primers were designed to separate species of earthworm and aphid. TGGE of the earthworm PCR products generated banding patterns that varied with haplotype in some species. Aphid and earthworm DNA could be detected in the guts of carabids for up to 24 h using TGGE. In P. melanarius, with low numbers of prey per insect gut (mean<3), interpretation of banding patterns proved to be tractable. Potential problems of interpretation of TGGE gels caused by multiple prey bands, cryptic bands, haplotype variation, taxonomic uncertainties (especially with regard to earthworms), secondary predation, scavenging and presence of parasites and parasitoids in the prey or the predators, are discussed. The results suggest that PCR, using combinations of general invertebrate and group-specific primers followed by TGGE, provides a potentially useful approach to the analysis of multiple uncharacterized prey in predators.


Inhibitory effect of blueberry polyphenolic compounds on oleic acid-induced hepatic steatosis in vitro.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide and is closely associated with metabolic syndromes, such as obesity, diabetes, and insulin resistance. Nonalcoholic fatty liver (NAFL), also called simple steatosis, is the initial phase of NAFLD, which is accompanied the characteristic pathological overaccumulation of lipids without inflammation. To prevent NAFLD from reaching the NAFL stage through dietary therapy, in the present work, wild Chinese blueberries (Vacciniun spp.) were selected for their well-known benefits in inhibiting metabolic syndrome. After being purified from wild Chinese blueberries, polyphenol-rich extracts were subsequently separated into three fractions, namely, anthocyanin-rich fraction, phenolic acid-rich fraction, and ethyl acetate extract. The inhibition of oleic acid (OA)-induced triglyceride (TG) deposition in HepG 2 cells was referred to as the potential activity of preventing NAFL. Biochemical indicators, such as cytotoxicity, TG level, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and intracellular reactive oxygen species, were used to evaluate the analogous pathological stage of NAFLD. The results show that OA ≤ 1.0 mM exhibits a dose-dependent induction of TG accumulation, and no inflammation was observed based on the changes in ALT and AST levels. Therefore, 1.0 mM OA was used to simulate an in vitro fatty liver. Blueberry polyphenol-rich extract efficiently inhibited OA-induced TG accumulation in HepG2 cells, and the phenolic acid-rich fraction performed efficiently. Seven phenolic acids were subsequently identified using a high-performance liquid chromatography assay, and the main types were caffeic, chlorogenic, ferulic, p-coumaric, and cinnamic acids. These phenolic acid standards also displayed good efficiency in inhibiting TG accumulation in HepG2 cells. These results imply that wild Chinese blueberries have a potential preventive effect on NAFLD in its early stage, and phenolic acids are the most efficient component.


Extension of the SIMLA package for generating pedigrees with complex inheritance patterns: environmental covariates, gene-gene and gene-environment interaction.
We have previously distributed a software package, SIMLA (SIMulation of Linkage and Association), which can be used to generate disease phenotype and marker genotype data in three-generational pedigrees of user-specified structure. To our knowledge, SIMLA is the only publicly available program that can simulate variable levels of both linkage (recombination) and linkage disequilibrium (LD) between marker and disease loci in general pedigrees. While the previous SIMLA version provided flexibility in choosing many parameters relevant for linkage and association mapping of complex human diseases, it did not allow for the segregation of more than one disease locus in a given pedigree and did not incorporate environmental covariates possibly interacting with disease susceptibility genes. Here, we present an extension of the simulation algorithm characterized by a much more general penetrance function, which allows for the joint action of up to two genes and up to two environmental covariates in the simulated pedigrees, with all possible multiplicative interaction effects between them. This makes the program even more useful for comparing the performance of different linkage and association analysis methods applied to complex human phenotypes. SIMLA can assist investigators in planning and designing a variety of linkage and association studies, and can help interpret results of real data analyses by comparing them to results obtained under a user-controlled data generation mechanism.A free download of the SIMLA package is available at http://wwwchg.duhs.duke.edu/software.


Management of abdominal endograft infection.
Incidence, clinical presentation and management of aortic grafts infection after open surgical repair are well described in the literature. Infective complications involving endografts after endovascular aneurysm repair (EVAR) have been scarcely investigated, since more attention has been given to the technical aspects of the procedure, including endoleaks, device migration, neck dilatation, endotension and aneurysm rupture. Nevertheless, that is a rare but severe complication occurring after EVAR; potentially difficult to diagnose and treat. Since 1991 only 102 cases of abdominal endograft infections have been reported in the literature. Treatment of infected abdominal endografts is controversial. Although reports have shown that high-risk patients with infected stent grafts treated conservatively with antimicrobial therapy and percutaneous drainage can still survive, most authors agree that an infected endograft should be removed if patient's conditions allow intervention. Standard treatment for infected abdominal endografts includes complete graft excision and local debridement followed by extra-anatomical bypass revascularization or in situ reconstruction with an aortic-bisiliac or bifemoral graft (Dacron or PTFE) or with a homograft. Lower overall mortality was observed for surgical management by explantation of infected endograft followed by in situ replacement as compared to other surgical solutions, but no definitive conclusions can be drawn about the optimal treatment strategy for aortic reconstruction.


The etiology of neonatal pneumonia, complicated by bronchopulmonary dysplasia.
The frequency of bronchopulmonary dysplasia (BPD) in preterm infants with a "ventilator-associated" pneumonia (VAP) ranges between 7 to 50%. To investigate the features of the etiological structure of neonatal pneumonia complicated by BPD, and to determine the sensitivity of pathogens to antibiotics. A retrospective chart review of 194 preterm infants with VAP, birth weight from 780 to 2820 g and gestational age from 27 to 37 weeks was conducted. A microbiological study of washings from the respiratory tract was conducted by standard qualitative and quantitative methods. Respiratory tract infections caused by E. coli (with hemolytic properties), Enterococcus spp. (with hemolytic properties), Pseudomonas aeruginosa, Stenotrophomonas maltophilia, various types of mycoplasmas, Staphylococcus aureus, and Candida krusei were found 4- 13 times more frequent in preterm infants with BPD than in preterm infants without BPD and more mature infants with or without this complication. BPD developed 7- 11 times more frequent in preterm infants with prolonged VAP and change in pathogens than in preterm infants with VAP without change of agent. BPD developed 5- 7 times more frequent in preterm infants with the association of pathogens than in preterm infants with a monoinfection. Massive colonization of respiratory tract pathogens by 1- 3 days of life (lg4 colony forming units in 1 ml and above) was an unfavorable prognostic factor for the development of VAP, complicated by BPD. The reduction in the frequency of BPD is might be possible with timeous and adequate antibacterial therapy of VAP.


Loss of CCDC6, the first identified RET partner gene, affects pH2AX S139 levels and accelerates mitotic entry upon DNA damage.
CCDC6 was originally identified in chimeric genes caused by chromosomal translocation involving the RET proto-oncogene in some thryoid tumors mostly upon ionizing radiation exposure. Recognised as a pro-apoptotic phosphoprotein that negatively regulates CREB1-dependent transcription, CCDC6 is an ATM substrate that is responsive to genotoxic stress. Here we report that following genotoxic stress, loss or inactivation of CCDC6 in cancers that carry the CCDC6 fusion, accelerates the dephosphorylation of pH2AX S139, resulting in defective G2 arrest and premature mitotic entry. Moreover, we show that CCDC6 depleted cells appear to repair DNA damaged in a shorter time compared to controls, based on reporter assays in cells. High-troughput proteomic screening predicted the interaction between the CCDC6 gene product and the catalytic subunit of Serin-Threonin Protein Phosphatase 4 (PP4c) recently identified as the evolutionarily conserved pH2AX S139 phosphatase that is activated upon DNA Damage. We describe the interaction between CCDC6 and PP4c and we report the modulation of PP4c enzymatic activity in CCDC6 depleted cells. We discuss the functional significance of CCDC6-PP4c interactions and hypothesize that CCDC6 may act in the DNA Damage Response by negatively modulating PP4c activity. Overall, our data suggest that in primary tumours the loss of CCDC6 function could influence genome stability and thereby contribute to carcinogenesis.


High-Performance Salt-Rejecting and Cost-Effective Superhydrophilic Porous Monolithic Polymer Foam for Solar Steam Generation.
Direct solar desalination with excellent solar photothermal efficiency, lower cost, and extended generator device lifetime is beneficial to increase potable water supplies. To address fundamental challenges in direct solar desalination, herein, we present a new and facile method for the scalable fabrication of the polymer porous foam (VMP) as salt-resistant photothermal materials, which was synthesized through a one-step hydrothermal method using styrene and 1-vinyl-3-ethylimidazolium tetrafluoroborate as monomers and N,N'-methylenebisacrylamide as the cross-linking agent. The as-resulted VMP shows excellent mechanical properties which could have a compression strain of 30%, resulting in its superior processability for practical operation. In addition, by taking advantage of its inherent low density, well-controlled porous structure (porosity is 73.81%), and extremely low thermal conductivity (0.03204 W m-1 K-1), the VMP exhibits an excellent solar evaporation property, and the solar photothermal efficiency can reach more than 88% under 1 kW m-2 irradiation. Moreover, the introduction of ionic liquid moiety (imidazolium tetrafluoroborate) into VMP results in its interesting superhydrophilic wettability, which can accelerate water transportation (wetting in 5s) and resolve the crystalline salt within 1.13 h. In addition, the interconnected macropores of the VMP, as water channels, can replenish the vaporized brine on the surface to prevent salt from adhering. The VMP shows a salt-resistant performance, for example, its solar evaporation efficiency remains nearly unchanged after 6 h duration under 1 sun irradiation. Based on its simple and cost-effective manufacturing process, excellent solar photothermal efficiency, and salt resistance, our VMP may be a promising candidate as photothermal materials for practical desalination from seawater and other wastewater.


Maternal, pregnancy and fetal outcomes in de novo anti-glomerular basement membrane antibody disease in pregnancy: a systematic review.
Outside of pregnancy, anti-glomerular basement membrane (GBM) antibody disease is associated with significant morbidity and mortality. However, there is limited knowledge regarding de novo anti-GBM disease in pregnancy. A systematic review was performed to identify maternal, pregnancy and fetal outcomes in de novo anti-GBM disease in pregnancy. Studies were selected from PubMed, EMBASE, Cochrane Library databases and conference proceedings, without language restriction. Data from eight patients were derived from seven case reports and one unpublished case. Most (6/8) patients presented after the first trimester. During pregnancy, acute kidney injury (5/8), anemia (5/8), hematuria (8/8) and proteinuria (8/8) were common. When hemodialysis was required antepartum (5/8), renal function recovery to independence of renal replacement was unlikely (2/5). While pulmonary involvement was common (5/8), no permanent damage was reported (0/8). The majority of cases ended in live births (6/8) although prematurity (6/6), intrauterine growth restriction (2/6), small for gestational age (4/6) and complications of prematurity (1/6) were common. When anti-GBM levels were tested in the living newborn, they were detectable (2/5), but no newborn renal or lung disease was reported (0/6). Complications in pregnancy included gestational diabetes (3/8), hyperemesis gravidarum (2/8) and preeclampsia (2/8). Live births can be achieved in de novo anti-GBM disease in pregnancy, but are commonly associated with adverse maternal, pregnancy and fetal outcomes. Only with awareness of common presentations, and management strategies can outcomes be optimized.


Characterization of the genetic diversity in superficial and systemic human isolates of Candida parapsilosis by randomly amplified polymorphic DNA (RAPD).
The application of randomly amplified polymorphic DNA (RAPD) technology for strain delineation of medically important yeasts has proved to be a valuable tool in clinico-epidemiological studies of Candida species. Candida parapsilosis, a form species of the fungi imperfecti, is an emerging pathogen gaining recognition as an opportunistic agent, especially in the immunocompromised. Therefore, 15 clinical isolates of C. parapsilosis obtained from oral, cutaneous and systemic Candida infections were typed by RAPD analysis using four different primers. The primers RSD6 and RSD9 elicited 7 genotypes each, whereas primers RSD7 and RSD12 revealed 6 and 10 genotypes, respectively. When the data were correlated, a higher degree of genomic heterogeneity in systemic isolates was noted compared with the oral and cutaneous isolates, which shared somewhat similar RAPD profiles. However, a single oral isolate (P5) and two systemic isolates (P13 and P15) elicited radically divergent profiles, dissimilar to their counterparts. RAPD study of the latter two isolates with three additional primers (RSD8, RSD10 and RSD11) confirmed the observed genomic disparity. These data substantiate the previous observations on the genomic heterogeneity in C. parapsilosis and point to genetic shifts which may be associated with ecodiversity, as well as the possible existence of distinct genetic groups within this form species.


Enolase isoenzymes in adult and developing Xenopus laevis and characterization of a cloned enolase sequence.
As part of a study of glycolysis during early development we have examined the pattern of expression of enolase isoenzymes in Xenopus laevis. In addition, the nucleotide sequence of a cDNA clone coding for the complete amino acid sequence of one enolase gene (ENO1) in X. laevis was determined. X. laevis ENO1 shows highest homology to mammalian non-neuronal enolase. Analysis of enolase isoenzymes in X. laevis by non-denaturing electrophoresis on cellulose acetate strips revealed five isoenzymes. One form was present in all tissues tested, two additional forms were expressed in oocytes, embryos, adult liver and adult brain, and two further forms were restricted to larval and adult muscle. Since enolase is a dimer, three different monomers (gene products) could account for the observed number of isoenzymes. This pattern of enolase isoenzyme expression in X. laevis differs from that of birds and mammals. In birds and mammals the most acidic form is neuron-specific and there is only one major isoenzyme expressed in the liver. RNAase protection experiments showed the presence of ENO1 mRNA in oocytes, liver and muscle, suggesting that it codes for a non-tissue-restricted isoenzyme. ENO1 mRNA concentrations are high in early oocytes, decrease during oogenesis and decrease further after fertilization. Enolase protein, however, is maintained at high concentrations throughout this period.


Mood and Anxiety Disorders Precede Development of Functional Gastrointestinal Disorders in Patients but Not in the Population.
Understanding the interactions between brain and gastrointestinal disorders requires analysis of the order of disease onset. We analyzed data from 2 independent studies to determine the proportion of individuals with diagnoses of functional gastrointestinal disorders (FGIDs) before diagnoses of mood or anxiety disorders (gut to brain), and vice versa (brain to gut). We collected data from a retrospective study of 4966 patients diagnosed with a FGID (irritable bowel syndrome, dyspepsia, or constipation) and mood or anxiety disorder at general practices in the United Kingdom (health care seekers) over an average period of 13.1 years; we recorded which diagnosis appeared first and compared these with patients' sex and socioeconomic factors. We also collected data from a population study of 1002 randomly selected individuals in Australia (non-heath care seekers) followed from 1997 through 2009; we determined whether subjects were free of either FGID or an anxiety or mood disorder at baseline but developed either one after a 12-year follow-up period. Among the 4966 health care seekers, 3279 patients were diagnosed with a mood or anxiety disorder before an FGID (ratio of 2:1). This ratio increased with socioeconomic disadvantage. The time period between diagnosis of mood or anxiety disorder and FGID was longer (median, 3.5 years) than time period between diagnosis of an FGID and a mood or anxiety disorder (median, 1.8 years). Among non-heath care seekers (population study), equal proportions were diagnosed with a mood or anxiety disorder before versus after an FGID. In an analysis of data from a study of patients and a population-based study of individuals with these diagnoses, we found 2-fold more patients to receive a diagnosis of a mood or anxiety disorder before an FGID, but equal proportions of individuals in the population to be diagnosed with the mood or anxiety disorder before versus after an FGID. Among patients, the mood or anxiety disorder was on average diagnosed more than 3 years before the FGID, offering opportunity for prevention. Our findings support a role for adverse socioeconomic factors in development of FGIDs in patients with psychological disorders.


Short, long, and beyond: molecular and embryological approaches to insect segmentation.
Over the past dozen years, studies comparing the expression of orthologues of the Drosophila segmentation genes among various insects have served to broaden our view of the ways in which insects make segments. The molecular data suggest that, although the overall genetic mechanisms of segmentation during embryogenesis have been conserved, the details of this process vary both within and between various insect orders. Here we summarize comparative gene expression data relevant to segmentation with an emphasis on understanding the extent of molecular patterning prior to gastrulation. These results are discussed in embryological context with an eye toward understanding the evolution of segmentation within insects.


Blood levels of alkylating metabolites of cyclophosphamide in the mouse after iv or oral administration.
Blood levels of cyclophosphamide (CPA) and its alkylating metabolites in mice were determined after iv or oral administration of a 200-mg/kg dose of radiolabeled CPA. Individual metabolites (4-hydroxy-CPA, 4-keto-CPA, alcophosphamide , dechloroethyl -CPA, carboxyphosphamide , and phosphoramide mustard) were isolated from blood by solvent extraction and by thin-layer chromatography. Area-under-the-blood-decay-curve (AUC) values were determined for CPA and its alkylating metabolites to provide a basis for comparison of systemic exposure by iv or oral treatment. The total AUC values for alkylating metabolites of CPA was observed to be greater after iv administration, and AUC values for each of the individual metabolites were greater after iv treatment, except for the minor metabolite alcophosphamide . The methods in this study have been applied to one patient to date and will be used in future studies with other patients to determine relative AUC values for the oncolytic CPA metabolites 4-hydroxy-CPA and phosphoramide mustard.


Prescribers' responses to alerts during medication ordering in the long term care setting.
Computerized physician order entry with clinical decision support has been shown to improve medication safety in adult inpatients, but few data are available regarding its usefulness in the long-term care setting. The objective of this study was to examine opportunities for improving medication safety in that clinical setting by determining the proportion of medication orders that would generate a warning message to the prescriber via a computerized clinical decision support system and assessing the extent to which these alerts would affect prescribers' actions. The study was set within a randomized controlled trial of computerized clinical decision support conducted in the long-stay units of a large, academically-affiliated long-term care facility. In March 2002, a computer-based clinical decision support system (CDSS) was added to an existing computerized physician order entry (CPOE) system. Over a subsequent one-year study period, prescribers ordering drugs for residents on three resident-care units of the facility were presented with alerts; these alerts were not displayed to prescribers in the four control units. We assessed the frequency of drug orders associated with various categories of alerts across all participating units of the facility. To assess the impact of actually receiving an alert on prescriber behavior during drug ordering, we calculated separately for the intervention and control units the proportion of the alerts, within each category, that were followed by an appropriate action and estimated the relative risk of an appropriate action in the intervention units compared to the control units. During the 12 months of the study, there were 445 residents on the participating units of the facility, contributing 3,726 resident-months of observation time. During this period, 47,997 medication orders were entered through the CPOE system-approximately 9 medication orders per resident per month. 9,414 alerts were triggered (2.5 alerts per resident-month). The alert categories most often triggered were related to risks of central nervous system side-effects such as over-sedation (20%). Alerts for risk of drug-associated constipation (13%) or renal insufficiency/electrolyte imbalance (12%) were also common. Twelve percent of the alerts were related to orders for warfarin. Overall, prescribers who received alerts were only slightly more likely to take an appropriate action (relative risk 1.11, 95% confidence interval 1.00, 1.22). Alerts related to orders for warfarin or central nervous system side effects were most likely to engender an appropriate action, such as ordering a recommended laboratory test or canceling an ordered drug. Long-term care facilities must implement new system-level approaches with the potential to improve medication safety for their residents. The number of medication orders that triggered a warning message in this study suggests that CPOE with a clinical decision support system may represent one such tool. However, the relatively low rate of response to these alerts suggests that further refinements to such systems are required, and that their impact on medication errors and adverse drug events must be carefully assessed.


Effects of the K+ channel activators, RP 52891, cromakalim and diazoxide, on the plasma insulin level, plasma renin activity and blood pressure in rats.
In normo- or hyperglycemic (i.v. infusion of 50 mg/kg/min glucose over 30 min) pithed rats, diazoxide (1 mg/kg/min i.v. over 20 min) significantly reduced plasma insulin content. By contrast, cromakalim, nicorandil or RP 52891 even at doses 40-fold higher than those producing the same hypotensive effect as diazoxide in intact anesthetized normotensive rats, failed to change insulin plasma levels. Glibenclamide (0.01-0.3 mg/kg i.v.) pretreatment antagonized dose-dependently the hypoinsulinemic activity of diazoxide with an i.v. ED50 value of 49 +/- 1 microgram/kg. In pithed rats, diazoxide increased markedly plasma renin activity. This effect was almost inhibited completely by 20 mg/kg i.v., but not at all by a 1-mg/kg i.v. dose of glibenclamide. In pentobarbital-anesthetized rats, diazoxide (0.5-2 mg/kg/min i.v. over 20 min) produced decreases in mean carotid artery blood pressure which were antagonized dose-dependently by glibenclamide (5-20 mg/kg i.v.). This sulfonylurea (20 mg/kg i.v.) also prevented the hypotensive effects of several i.v. administered K+ channel activators (cromakalim, RP 52891 and nicorandil) but not those of numerous hypotensive agents such as acetylcholine, adenosine, bradykinin, clonidine, histamine, salbutamol, dihydralazine, papaverine, platelet aggregating factor, nitroglycerin, nitroprusside, nitrendipine and diltiazem. Although glibenclamide lowered plasma glucose levels, its blocking activity vis-à-vis the hypotension evoked by cromakalim was not affected when its hypoglycemic effects were reversed with an i.v. injection of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)


Measuring Gambling Harm: The Influence of Response Scaling on Estimates and the Distribution of Harm Across PGSI Categories.
Recent research has shown that harm is not just a feature of problem gambling, but can also be observed in other lower risk categories. Some debates exist, however, as to the distribution of harm across these categories and how harm should be best measured. This study was designed to examine how estimates of self-reported harm are affected by the methodology used. A particular focus was on how harm estimates for low and higher risk gambling (as classified by the PGSI) varied when respondents were able to make more graded attributions of their harm to gambling. An online panel sample of 554 gamblers responded to a brief survey that included the PGSI, measures of gambling harm drawn from Browne et al. (Assessing gambling-related harm in Victoria: a public health perspective, Victorian Responsible Gambling Foundation, Melbourne, 2016) as well as questions about demographics and gambling habits. The recruitment was designed to obtain good representation of each PGSI group, with 23% found to be problem gamblers; 36% moderate risk and 21% low risk gamblers. In support of Browne et al. (2016), the findings showed that higher proportions of harm in low risk gamblers is likely to be identified when one uses binary or 'any harm' scoring, but that this effect mostly disappears when more graded scoring or attribution of harm measures are used. Higher risk PGSI groups consistently reported more harms and more serious harms than lower risk groups. It was concluded that the measurement of gambling harm and its estimated distribution over PGSI categories is quite sensitive to how it is measured.


Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis.
Evaluation of transcriptional changes in the striatum may be an effective approach to understanding the natural history of changes in expression contributing to the pathogenesis of Huntington disease (HD). We have performed genome-wide expression profiling of the YAC128 transgenic mouse model of HD at 12 and 24 months of age using two platforms in parallel: Affymetrix and Illumina. The data from these two powerful platforms were integrated to create a combined rank list, thereby revealing the identity of additional genes that proved to be differentially expressed between YAC128 and control mice. Using this approach, we identified 13 genes to be differentially expressed between YAC128 and controls which were validated by quantitative real-time PCR in independent cohorts of animals. In addition, we analyzed additional time points relevant to disease pathology: 3, 6 and 9 months of age. Here we present data showing the evolution of changes in the expression of selected genes: Wt1, Pcdh20 and Actn2 RNA levels change as early as 3 months of age, whereas Gsg1l, Sfmbt2, Acy3, Polr2a and Ppp1r9a RNA expression levels are affected later, at 12 and 24 months of age. We also analyzed the expression of these 13 genes in human HD and control brain, thereby revealing changes in SLC45A3, PCDH20, ACTN2, DDAH1 and PPP1R9A RNA expression. Further study of these genes may unravel novel pathways contributing to HD pathogenesis. DDBJ/EMBL/GenBank accession no: GSE19677.


Moment measurement accuracy of a parallel spherical robot for dynamic posturography.
This paper characterizes the moment measurement accuracy for a novel parallel spherical robot (SR) for dynamic posturography, controllable by position or impedance. The SR consists of three linear motors placed on a support base, a moving base, and three passive arms equipped with uniaxial load cells permitting impedance controlled perturbations. To evaluate the accuracy, a subject stood still on the SR, set in position control mode, while selected sinusoidal trajectories were applied. The moments computed by the load cells were compared to the value measured by a six-component force platform, placed on top of the rotating base. For the intended application of the SR, the errors were negligible with the worse case of only 4 Nm in a total of 15 trials (five conditions, three repetitions). The observed moment error was related mainly to the intrinsic accuracy of the sensors, equal to about 7 N. To demonstrate clinical applicability, the platform was set to impedance control mode and a protocol was tested with a 12-year-old girl with brain injury and a group of four healthy subjects. In total, 24 trials (eight conditions, three repetitions) were recorded for each subject. The results of this pilot study identified distinctive postural behaviors and therefore showed that the SR can be considered as an effective tool for dynamic posturography.


Measurement and analysis of nicotine and other VOCs in indoor air as an indicator of passive smoking.
In Finland the Tobacco Act was amended in 1994 to include workplaces. The developed method for estimating passive smoking, or environmental tobacco smoke utilised the widely used measurement of volatile organic compounds in indoor air quality surveys. The method is based on active sorbent sampling, thermal desorption and gas chromatography/mass selective detection (GC/MS) analysis and it has been tested in a chamber and in field conditions. The method can be used simultaneously to measure volatile organic compounds and exposure to tobacco smoke. We recommend nicotine, collected by active sampling, as an indicator for the evaluation of the exposure to environmental tobacco smoke spreading from smoking areas.


Could -79 °C Spray-Type Cryotherapy Be an Effective Monotherapy for the Treatment of Keloid?
Cryotherapy has been regarded as an effective modality for the treatment of keloids, and the spray-type device is one of the novel cryotherapeutic units. However, the biological mechanisms and therapeutic effects of this technique are incompletely studied. We evaluated the clinical efficacy of our cryotherapy protocol with molecular and pathologic evidence for the treatment of keloids. We evenly split each of ten keloid lesions into a non-treated (C-) and treated (C+) area; the C+ area was subjected to two freeze-thaw cycles of spray-type cryotherapy using -79 °C spray-type CryoPen™. This treatment was repeated after an interval of two weeks. The proliferation and migration abilities of the fibroblasts isolated from the dermis under the cryotherapy-treated or untreated keloid tissues (at least 5 mm deep) were compared and pathologic findings of the full layer were evaluated. Molecular analysis revealed that the number of dermal fibroblasts was significantly higher in C+ group as compared with C- group. The dermal fibroblasts from C+ group showed more than two-fold increase in the migration ability as compared with the fibroblasts from C- group. The expression of matrix metallopeptidase 9 was increased by more than two-fold and a significant increase in transforming growth factor beta 1 expression and Smad2/3 phosphorylation level was observed in C+ group. C+ group showed more extensive lymphoplasmacytic infiltration with thicker fibrosis and occasional "proliferating core collagen" as compared with C- group. Thus, -79 °C spray-type cryotherapy is ineffective as a monotherapy and should be used in combination with intralesional corticosteroids or botulinum toxin A for favourable outcomes in the treatment of thick keloids.


Improved Oxygen Activation over a Carbon/Co3O4 Nanocomposite for Efficient Catalytic Oxidation of Formaldehyde at Room Temperature.
Oxygen activation is a key step in the catalytic oxidation of formaldehyde (HCHO) at room temperature. In this study, we synthesized a carbon/Co3O4 nanocomposite (C-Co3O4) as a solution to the insufficient capability of pristine Co3O4 (P-Co3O4) to activate oxygen for the first time. Oxygen activation was improved via carbon preventing the agglomeration of Co3O4 nanoparticles, resulting in small particles (approximately 7.7 nm) and more exposed active sites (oxygen vacancies and Co3+). The removal efficiency of C-Co3O4 for 1 ppm of HCHO remained above 90%, whereas P-Co3O4 was rapidly deactivated. In static tests, the CO2 selectivity of C-Co3O4 was close to 100%, far exceeding that of P-Co3O4 (42%). Various microscopic analyses indicated the formation and interaction of a composite structure between the C and Co3O4 interface. The carbon composite caused a disorder on the surface lattice of Co3O4, constructing more oxygen vacancies than P-Co3O4. Consequently, the surface reducibility of C-Co3O4 was improved, as was its ability to continuously activate oxygen and H2O into reactive oxygen species (ROS). We speculate that accelerated production of ROS helped rapidly degrade intermediates such as dioxymethylene, formate, and carbonate into CO2. In contrast, carbonate accumulation on P-Co3O4 surfaces containing less ROS may have caused P-Co3O4 inactivation. Compared with noble nanoparticles, this study provides a transition metal-based nanocomposite for HCHO oxidation with high efficiency, high selectivity, and low cost, which is meaningful for indoor air purification.


Antidepressant exposure as a predictor of clinical outcomes in the Treatment of Resistant Depression in Adolescents (TORDIA) study.
This paper examines the relationship between plasma concentration of antidepressant and both clinical response and adverse effects in treatment-resistant depressed adolescents. Adolescents (n = 334) with major depression who had not responded to a selective serotonin reuptake inhibitor (SSRI) were randomized to 1 of 4 treatments: switch to another SSRI (fluoxetine, citalopram, or paroxetine), switch to venlafaxine, switch to SSRI plus cognitive behavior therapy, or switch to venlafaxine plus cognitive behavior therapy. Adolescents who did not improve by 6 weeks had their dose increased. Plasma concentrations of medication and metabolites were measured at 6 weeks in 244 participants and at 12 weeks in 204 participants. Adolescents treated with citalopram whose plasma concentration was equal to or greater than the geometric mean (GM) showed a higher response rate compared to those with less than the GM, with parallel but nonsignificant findings for fluoxetine. A dose increase of citalopram or fluoxetine at week 6 was most likely to result in response when it led to a change in concentration from less than the GM at 6 weeks to the GM or greater at week 12. Plasma levels of paroxetine, venlafaxine, or O-desmethylvenlafaxine were not related to clinical response. Exposure was associated with more cardiovascular and dermatologic side effects in those receiving venlafaxine. Antidepressant concentration may be useful in optimizing treatment for depressed adolescents receiving fluoxetine or citalopram.


How useful is antireflux surgery in lung transplant patients with gastroesophageal reflux?
Respiratory function deteriorates over time after lung transplant. Reflux disease with pulmonary complications is a possible cause of this decline. This case series we aim to assess whether respiratory function improves after Nissen fundoplication in lung transplant patients and if surgery reduces gastroesophageal reflux disease (GERD) symptoms and use of proton pump inhibitors (PPIs). A retrospective case series of lung transplant patients with reflux disease and Nissen fundoplication. Clinical symptoms, pH-metry data, use of PPIs were recorded before the procedure and up to 18 months postoperatively. The FEV1 values before and after Nissen fundoplication were recorded at 3 monthly intervals. Patients' satisfaction scores were recorded before operation and postoperatively. A total of 64 lung transplant patients were selected. After Nissen fundoplication, the pH studies were done on 26 patients. The mean overall acid exposure fraction was 1.03% (P<0.05). FEV1 declined for 6 months postoperatively and then gradually improved. The comparison of FEV1 at 3 months preoperatively to 3 months postoperatively showed no significant difference (P=0.067) as well as at 6 months. A significant improvement in clinical GERD symptoms was achieved after antireflux surgery; however, the patients remained receiving PPIs. NF has been established as a safe operation for lung transplant patients. Late Nissen fundoplication did not improve lung function significantly amongst lung transplanted patients; however, patients with symptomatic GERD may have benefited from Nissen fundoplication in terms of symptom relief. A multicenter randomized control trial is needed to assess the effect of early unselected reflux control on respiratory function and graft survival.


COVIDOSE: Low-dose tocilizumab in the treatment of Covid-19.
Background Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the high mortality of coronavirus disease 2019 (Covid-19). Tocilizumab, an IL-6 receptor blocking monoclonal antibody, has been repurposed for Covid-19, but prospective trials and dose-finding studies in Covid-19 are lacking. Methods We conducted a phase 2 trial of low-dose tocilizumab in hospitalized adult patients with Covid-19, radiographic pulmonary infiltrate, fever, and C-reactive protein (CRP) >= 40 mg/L who did not require mechanical ventilation. Dose cohorts were determined by a trial Operations Committee, stratified by CRP and epidemiologic risk factors. A range of doses from 40 to 200 mg (low-dose tocilizumab) was evaluated, with allowance for one repeat dose at 24-48 hours. The primary objective was to assess the relationship of dose to fever resolution and CRP response. Outcomes were compared with retrospective controls with Covid-19. Correlative studies evaluating host antibody response were performed in parallel. Findings A total of 32 patients received low-dose tocilizumab. This cohort had improved fever resolution (75.0% vs. 34.2%, p = 0.001) and CRP decline (86.2% vs. 14.3%, p < 0.001) in the 24-48 hours following drug administration, as compared to the retrospective controls (N=41). The probabilities of fever resolution or CRP decline did not appear to be dose-related in this small study (p=0.80 and p=0.10, respectively). Within the 28-day follow-up, 5 (15.6%) patients died. For patients who recovered, median time to clinical recovery was 3 days (IQR, 2-5). Clinically presumed and/or cultured bacterial superinfections were reported in 5 (15.6%) patients. Correlative biological studies demonstrated that tocilizumab-treated patients produced anti-SARS-CoV-2 antibodies comparable to controls. Interpretation Low-dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with Covid-19. Results of this trial and its correlative biological studies provide rationale for a randomized, controlled trial of low-dose tocilizumab in Covid-19.


Lower body negative pressure and effects of autonomic heart blockade on cardiovascular responses.
Heart rate, arterial pressure and cardiac output were recorded in eight healthy male volunteers during exposure to 80 mmHg of lower body negative pressure (LBNP) in the supine position before and after beta-adrenergic and combined beta-adrenergic and parasympathetic blockade of the heart as induced by the i.v. administration of propranolol 0.25 mg/kg b.wt. and atropine 0.04 mg/kg b.wt. After propranolol, heart rate response to LBNP averaged 48% of that observed without blockade indicating that LBNP-induced cardioacceleration is of both sympathetic and parasympathetic origin. Tolerance to LBNP was reduced by beta-adrenergic blockade, since the decrease in mean arterial pressure during LBNP was exaggerated by such blockade. Although the addition of atropine markedly elevated mean arterial pressure and cardiac output in the control situation, tolerance to LBNP was not enhanced by this drug as judged from the arterial pressure response. Post-LBNP overshoot in mean arterial pressure was strikingly augmented by combined cardiac effector blockade and was in part due to a lingering elevation of total peripheral resistance, cardiac output remaining decreased for more than 110 s after release of LBNP.


Quasicontinuous Cooperative Adsorption Mechanism in Crystalline Nanoporous Materials.
The hase behavior of confined fluids adsorbed in nanopores differs significantly from their bulk counterparts and depends on the chemical and structural properties of the confining structures. In general, phase transitions in nanoconfined fluids are reflected in stepwise adsorption isotherms with a pronounced hysteresis. Here, we show experimental evidence and an in silico interpretation of the reversible stepwise adsorption isotherm which is observed when methane is adsorbed in the rigid, crystalline metal-organic framework IRMOF-1 (MOF-5). In a very narrow range of pressures, the adsorbed fluid undergoes a structural and highly cooperative reconstruction and transition between low-density and high-density nanophases, as a result of the competition between the fluid-framework and fluid-fluid interactions. This mechanism evolves with temperature: below 110 K, a reversible stepwise isotherm is observed, which is a result of the bimodal distribution of the coexisting nanophases. This temperature may be considered as a critical temperature of methane confined to nanopores of IRMOF-1. Above 110 K, as the entropy contribution increases, the isotherm shape transforms to a common continuous S-shaped form that is characteristic to a gradual densification of the adsorbed phase as the pressure increases.


Reproductive parameters of female Macaca mulatta tcheliensis in the temperate forest of Mount Taihangshan, Jiyuan, China.
The remaining population of Macaca mulatta tcheliensis, approximately 3,000 individuals, is currently confined to the southern region of Mount Taihangshan, northern China. Using data collected from February 2003 to November 2012, we examined female reproductive characteristics in a seasonally food supplemented free-ranging group of M. m. tcheliensis (Wangwu 1, WW-1), inhabiting the Taishangshan Macaque National Nature Reserve (TMNNR), Jiyuan, China. We tested a series of predictions regarding the degree to which M. m. tcheliensis is best considered as a "strict income breeder," a "relaxed income breeder" or a "capital breeder." This group was comprised 18 adult females who produced 64 infants over the 10-year study period. In our study group (WW-1) adult female macaques gave birth to an average of 0.71 ± 0.26 infants per year. Infant mortality was 13.4 ± 19.3%. The age at first birth for mothers was 4.9 ± 0.5 years old. The mean inter-birth interval (IBI) was 15.4 ± 4.9 months. Based on the fact M. m. tcheliensis is a strictly seasonal breeder (76.6% of births occurred between April and May) with infants born during a time of the year when food availability appears to be high, and that their IBI is intermediate in length compared with other macaque populations, our results suggest that M. m. tcheliensis follows a birth pattern most consistent with a "relaxed income breeder" strategy.


Structural analysis and potential immunostimulatory activity of Nannochloropsis oculata polysaccharides.
The relevance of microalgae biotechnology for producing high-value compounds with biomedical application, such as polysaccharides, has been increasing. Despite this, the knowledge about the composition and structure of microalgae polysaccharides is still scarce. In this work, water-soluble polysaccharides from Nannochloropsis oculata were extracted, fractionated, structurally analysed, and subsequently tested in terms of immunostimulatory activity. A combination of sugar and methylation analysis with interaction data of carbohydrate-binding proteins using carbohydrate microarrays disclosed the complex structural features of the different polysaccharides. These analyses showed that the water-soluble polysaccharides fractions from N. oculata were rich in (β1→3, β1→4)-glucans, (α1→3)-, (α1→4)-mannans, and anionic sulphated heterorhamnans. The immunostimulatory assay highlighted that these fractions could also stimulate murine B-lymphocytes. Thus, the N. oculata water-soluble polysaccharides show potential to be further explored for immune-mediated biomedical applications.


[Kikuchi's necrotizing lymphadenitis. A clinical case].
We present a case of a female patient who presented with Kikuchi's necrotic lymphadenitis a rare disease in our country and whose diagnosis fundamentally is histological, which itself is also difficult because of the wide range of differential diagnosis which has to be considered. This entity is frequent during the adolescent period in females and its clinical manifestations are few apart from that related to the lymphadenitis.


The giant cell in cholesterol resorption.
Giant cells in the experimental cholesterol granuloma provided a convenient, recognizable cellular model in which to follow the transformation of crystalline cholesterol to liquid lipid. Crystals that were too large to be ingested by individual macrophages were incorporated into a multinucleate cell by a process of circumfusion, and were progressively converted to cholesterol esters within the giant cell. The liquid ester droplets seemed then to be mobilized by mononuclear cells until the entire implant had been resorbed.


Avian pneumovirus infection in Minnesota turkeys: experimental reproduction of the disease.
Avian pneumovirus (APV) is an emerging viral respiratory disease agent of turkeys in Minnesota. Clinical signs of APV infection include open mouth breathing, ocular and nasal discharge, and swelling of infraorbital sinuses. The virus spreads rapidly among flocks of susceptible turkeys and is associated with increased mortality rates. A flock of 11-wk-old turkeys experienced a respiratory problem characterized by coughing, sneezing, swollen sinuses, and nasal discharge. The reverse transcriptase-polymerase chain reaction (RT-PCR) performed on tissues from the nasal turbinates and tracheal tissues was positive for avian pneumovirus. Turbinate tissue was inoculated into chicken embryo fibroblasts, and cytopathic effect was observed after five blind passages. In an attempt to reproduce the disease, 50 microl of this cell culture-propagated virus was instilled into each conjunctival space and nostril of 23-day-old turkey poults. The poults were sacrificed at 2-day intervals for 12 days, and serum, tissues, and tracheal and cloacal swabs were collected. Between days 2 and 10 after exposure, the poults developed ocular and nasal discharge and swollen sinuses. The virus was detected by RT-PCR and virus isolation from the nasal turbinates of poults sacrificed on days 4 and 6 postinoculation. Antibodies to APV were detected by enzyme-linked immunosorbent assay.


Polygenic Multiple Sclerosis Risk and Population-Based Childhood Brain Imaging.
Multiple sclerosis (MS) is a neurological disease with a substantial genetic component and immune-mediated neurodegeneration. Patients with MS show structural brain differences relative to individuals without MS, including smaller regional volumes and alterations in white matter (WM) microstructure. Whether genetic risk for MS is associated with brain structure during early neurodevelopment remains unclear. In this study, we explore the association between MS polygenic risk scores (PRS) and brain imaging outcomes from a large, population-based pediatric sample to gain insight into the underlying neurobiology of MS. We included 8- to 12-year-old genotyped participants from the Generation R Study in whom T1-weighted volumetric (n = 1,136) and/or diffusion tensor imaging (n = 1,088) had been collected. PRS for MS were calculated based on a large genome-wide association study of MS (n = 41,505) and were regressed on regional volumes, global and tract-specific fractional anisotropy (FA), and global mean diffusivity using linear regression. No associations were observed for the regional volumes. We observed a positive association between the MS PRS and global FA (β = 0.098, standard error [SE] = 0.030, p = 1.08 × 10-3 ). Tract-specific analyses showed higher FA and lower radial diffusivity in several tracts. We replicated our findings in an independent sample of children (n = 186) who were scanned in an earlier phase (global FA; β = 0.189, SE = 0.072, p = 9.40 × 10-3 ). This is the first study to show that greater genetic predisposition for MS is associated with higher global brain WM FA at an early age in the general population. Our results suggest a preadolescent time window within neurodevelopment in which MS risk variants act upon the brain. ANN NEUROL 2020;87:774-787.


Keratin 20 serine 13 phosphorylation is a stress and intestinal goblet cell marker.
Keratin polypeptide 20 (K20) is an intermediate filament protein with preferential expression in epithelia of the stomach, intestine, uterus, and bladder and in Merkel cells of the skin. K20 expression is used as a marker to distinguish metastatic tumor origin, but nothing is known regarding its regulation and function. We studied K20 phosphorylation as a first step toward understanding its physiologic role. K20 phosphorylation occurs preferentially on serine, with a high stoichiometry as compared with keratin polypeptides 18 and 19. Mass spectrometry analysis predicted that either K20 Ser(13) or Ser(14) was a likely phosphorylation site, and Ser(13) was confirmed as the phospho-moiety using mutation and transfection analysis and generation of an anti-K20-phospho-Ser(13) antibody. K20 Ser(13) phosphorylation increases after protein kinase C activation, and Ser(13)-to-Ala mutation interferes with keratin filament reorganization in transfected cells. In physiological contexts, K20 degradation and associated Ser(13) hyperphosphorylation occur during apoptosis, and chemically induced mouse colitis also promotes Ser(13) phosphorylation. Among mouse small intestinal enterocytes, K20 Ser(13) is preferentially phosphorylated in goblet cells and undergoes dramatic hyperphosphorylation after starvation and mucin secretion. Therefore, K20 Ser(13) is a highly dynamic protein kinase C-related phosphorylation site that is induced during apoptosis and tissue injury. K20 Ser(13) phosphorylation also serves as a unique marker of small intestinal goblet cells.


Calcium distribution in Amoeba proteus.
A preliminary investigation of the distribution of cellular calcium in Amoeba proteus was undertaken. Total cellular calcium under control conditions was found to be 4.59 mmol/kg of cells. When the external Ca++ concentration is increased from the control level of 0.03 to 20 mM, a net Ca++ influx results with a new steady-state cellular calcium level being achieved in integral of 3 h. At steady state the amount of calcium per unit weight of cells is higher than the amount of calcium per unit weight of external solution when the external concentration of Ca++ is below 10 mM. At external Ca++ concentrations above this level, total cellular calcium approaches the medium level of Ca++. Steady-state calcium exchange in Amoeba proteus was determined with 45Ca. There is an immediate and rapid exchange of integral of 0.84 mmol/kg of cells or 18% of the total cellular calcium with the labelled Ca++. Following this initial exchange, there was very little if any further exchange observed. Most of this exchanged calcium could be eliminated from the cell with 1 mM La+++, suggesting that the exchanged calcium is associated with the surface of the cell. Increase in either the external Ca++ concentration of pH raise the amount of exchangeable calcium associated with the cell. Calcium may be associated with the cell surface as a co-ion in the diffuse double layer or bound to fixed negative sites on the surface of the cell. If Ca++-binding sites do exist on the cell surface, there may be more than one type and they may have different dissociation constants. The cytoplasmic Ca++ ion activity is probably maintained at very low levels.


Relapsing neuromyelitis optica and relapsing-remitting multiple sclerosis: differentiation at diffusion-tensor MR imaging of corpus callosum.
To prospectively assess sensitivity and specificity of diffusion indexes of the corpus callosum (CC) for differentiating relapsing neuromyelitis optica (RNMO) from relapsing-remitting multiple sclerosis (RRMS), by using final clinical diagnosis as the reference standard. Participants provided informed consent; the study was approved by the institutional review board. Forty-six consecutive patients with RRMS (18 men, 28 women; mean age, 37.7 years; range, 18-58 years) and 26 consecutive patients with RNMO (two men, 24 women; mean age, 38.6 years; range, 19-59 years) underwent diffusion-tensor magnetic resonance imaging. Mean diffusivity (MD) and fractional anisotropy (FA) of the region of interest (ROI) of the CC in the midsagittal plane were measured and used as discriminative indexes. Bayesian classification with leave-one-out cross-validation was used to determine diagnostic accuracy. Differences in diffusion indexes of ROIs among groups were evaluated by using the Kruskal-Wallis test, followed by the Mann-Whitney U test for multiple comparisons and Bonferroni correction. Mean MD (8.48 x 10(-4) mm(2)/sec) and FA (0.729) of the ROI in patients with RNMO were significantly (P<.001) different from those (MD=10.64 x 10(-4) mm(2)/sec, FA=0.599) in patients with RRMS. Sensitivity and specificity for differentiation were 92.3% (24 of 26 patients with RNMO) and 93.5% (43 of 46 patients with RRMS) for FA and 88.5% (23 of 26 patients with RNMO) and 89.1% (41 of 46 patients with RRMS) for MD, respectively. Measurement of diffusion indexes of the CC may be useful for distinguishing patients with RNMO from those with RRMS.


Malignant hyperthermia in a dog: case report and review of the syndrome.
Malignant hyperthermia occurred in an adult Greyhound 24 hours after narcotic anesthesia and surgery. Stress was considered the most likely cause. Treatment with dantrolene, in conjunction with cooling techniques and other symptomatic and supportive therapy, was successful.


Dynamics of non-communicable disease prevention, diagnosis and control in Lebanon, a fragile setting.
Non-communicable diseases (NCD) present an increasing global health challenge, particularly for settings affected by fragility where access to care may be disrupted, and where high-quality continuous care delivery is difficult to achieve. This study documents the complex dynamics of NCD prevention and management in the fragile setting of rural Beqaa, Lebanon. Participatory system dynamics methods were used, including 30 semi-structured interviews and three Group Model Building (GMB) workshops. Participants included health care providers offering NCD care, and Lebanese host- and Syrian refugees community members affected by NCDs. Participants across all groups articulated a shared complex understanding of both the structural and direct determinants behind NCD onset. Lebanese and Syrian community members further identified several barriers to health seeking, including restrictions in health coverage, limited availability of services in the Beqaa and perceptions of poor-quality care. Health providers and community members described a health system overtly focused on disease control and overwhelmed by delivery of care to people living with NCD across both communities. Participants across all groups agreed on the need for health promotion and primary prevention activities and identified priority interventions in these areas.


A unified ligand electronic parameter based on 13C NMR spectroscopy of N-heterocyclic carbene complexes.
The properties and reactivities of transition metal complexes are rooted in the stereoelectronic properties of their ligands. While the bulk of a ligand can be easily evaluated and compared by the drawing of its Lewis structure, prediction on the electronic contributions is often less straightforward. Thus, several electronic parameters have been developed for the experimental evaluation of ligands throughout the years. This article accounts for the most recent one developed by the Huynh group, which employs 13C NMR spectroscopy to determine ligand donor strengths using N-heterocyclic carbene complexes. This parameter not only proves to be safer, more convenient and accurate in comparison to existing methodologies, but it also provides, in certain cases, more intuitive and reliable results. Furthermore, it is currently the only one that allows the direct comparison of various Werner-type and organometallic ligands on a unified scale.


Nebulised steroid in the treatment of croup: a systematic review of randomised controlled trials.
Croup is one of the commonest respiratory complaints among children. There is growing evidence that steroids may be an effective treatment. To assess the effectiveness of treatment with nebulised steroid for children with croup. Systematic review of randomised controlled trials comparing administration of nebulised steroid with placebo. Trials were identified from searches of three bibliographic databases, the Cochrane Controlled Trials Register, correspondence with the manufacturers of nebulised steroid, and one round of manual citation searching. Eight randomised controlled trials were identified including 574 children with mild to severe croup. Overall, the mean age was 25.2 months and 72% of children were male. All trials were hospital-based and of good methodological quality, with adequate concealment of treatment allocation and blind outcome assessment. Children treated with nebulised steroid were significantly more likely to show an improvement in croup score by five hours (combined relative risk = 1.48, 95% confidence interval [CI] = 1.27 to 1.74) and significantly less likely to need hospital admission after attending the emergency department (combined relative risk = 0.56, 95% CI = 0.42 to 0.75) than the placebo group. The funnel plot indicated the presence of publication bias, with smaller studies showing the larger effects, but this could also be owing to less pronounced effects in studies of older children with milder croup. Nebulised steroids are effective in the treatment of children attending hospital departments with croup. A meta-analysis based on individual patient data could clarify to what extent the effect depends on age and severity of disease. New trials are needed to define the indications for, and effectiveness of, steroid treatment of croup in the community.


MiR-200a inhibits cell proliferation and EMT by down-regulating the ASPH expression levels and affecting ERK and PI3K/Akt pathways in human hepatoma cells.
The primary objective of this study was to investigate the role of miR-200a in cell proliferation and epithelial-mesenchymal transition (EMT) through regulating targeting aspartate-β-hydroxylase (ASPH), which may further affect the activation of ERK/PI3K/Akt pathway. Liver cancer and adjacent tissues were collected from 72 cases of liver cancer patients with surgery in our hospital. In this study, the mRNA expression level of miR-200a was significantly decreased by real-time PCR (RT-PCR) detection. ASPH expressions, however, had an opposite tendency compared to that of miR-200a. We found a significantly negative correlation between miR-200a expressions and ASPH expressions. The survival rate of liver cancer patients with the low expressed ASPH was significantly higher than those with the high expressed ASPH. RT-PCR and Western blot results showed that low expressed miR-200a and highexpressed ASPH were found in liver cancer cell lines. Further research discovered that miR-200a transfection could significantly decrease the relative luciferase activity when it was integrated with ASPH 3'-untranslated region (3'-UTR) in HepG2 cells. Cell Counting Kit (CCK-8) detection showed that treatment with miR-200a mimics reduced cell viability, while the over-expressed ASPH increased cell viability by regulating the c-mycmrna (c-Myc) and Cyclin-D1 expressions. The EMT-related genes including E-Cadherin, N-Cadherin and Vimentin expressions were significantly increased, whereas the over-expressed ASPH exerted the opposite effects. In addition, extracellular signal regulated kinase (ERK), phosphoinositide-3-kinase (PI3K) and serine threonine kinase (AKT) were suppressed by miR-200a mimics. In conclusion, miR-200a inhibits cell proliferation and EMT in human hepatoma cells by targeting ASPH and affecting ERK and PI3K/Akt signaling pathways.


Assessment of dentists' awareness and knowledge levels on the Novel Coronavirus (COVID-19).
Coronavirus disease-2019 (COVID-19) is the most recent infectious disease that is spreading rapidly throughout the world. This study aimed to evaluate the knowledge and awareness levels of dentists on COVID-19. This survey study, consisting of 37 questions, was sent to dentists via an online link in the first two weeks of April 2020. The questionnaire consisted of questions related to the knowledge level of dentists on COVID-19 during the pandemic period. The knowledge level of dentists was assessed with a 24-point scoring, consisting of correct answers. A Chi-square test was used to compare qualitative data (p < 0.05). A total of 267 dentists participated in this study, of which 51.7% were aged under 30 years, and 67% were women. The participants' knowledge level means score was 19.03 ± 3.15. According to these results, 231 were determined (86.5%) as high knowledgeable. Positive associations between increased knowledge level and factors such as being a woman, working in a university hospital, and being informed outside the institution were determined. The knowledge level of the dentists working in Istanbul about the COVID-19 pandemic is quite high.


On methods of inhomogeneity corrections for photon transport.
Eight methods of photon inhomogeneity correction were examined for their photon transport approximations. The methods were categorized according to the different approaches used to model scatter photon dose contribution. They were the ratio of TAR (RTAR) and the modified Batho power law which utilized only the 1-D density information along the primary photon path; the equivalent TAR (ETAR) and the FFT convolution methods which incorporated the 3-D density information of the medium for empirical scatter dose calculation; the differential SAR (DSAR), the delta volume (DV), dose spread array (DSA), and differential pencil beam (DPB) methods which employed explicit 3-D scatter ray-trace calculation. Cobalt-60 measurements in horizontal slab phantoms were used to allow simpler data analysis. RTAR consistently overestimated lung corrections by approximately 10%. The scatter ray-trace approach was not always better as the DSAR calculations were inferior to those using the Batho method. The ray-tracing DV, DPB, and DSA methods agreed with measurements mostly to within 2%, at the expense of long computation time. The nonscatter ray-tracing ETAR and FFT convolution calculations were only slightly inferior in the same geometries. These methods improve on the current 1-D methods and should be seriously considered for fast optimization purposes in practical 3-D treatment planning.


Coordinated hedgehog signaling induces new hair follicles in adult skin.
Hair follicle (HF) development is orchestrated by coordinated signals from adjacent epithelial and mesenchymal cells. In humans this process only occurs during embryogenesis and viable strategies to induce new HFs in adult skin are lacking. Here, we reveal that activation of Hedgehog (Hh) signaling in adjacent epithelial and stromal cells induces new HFs in adult, unwounded dorsal mouse skin. Formation of de novo HFs recapitulated embryonic HF development, and mature follicles produced hair co-occurring with epithelial tumors. In contrast, Hh-pathway activation in epithelial or stromal cells alone resulted in tumor formation or stromal cell condensation respectively, without induction of new HFs. Provocatively, adjacent epithelial-stromal Hh-pathway activation induced de novo HFs also in hairless paw skin, divorced from confounding effects of pre-existing niche signals in haired skin. Altogether, cell-type-specific modulation of a single pathway is sufficient to reactivate embryonic programs in adult tissues, thereby inducing complex epithelial structures even without wounding.


Polymer nanocomposites: structure, interaction, and functionality.
This feature article discusses the main factors determining the properties of polymer nanocomposites with special attention paid to structure and interactions. Usually more complicated structure develops in nanocomposites than in traditional particulate filled polymers, and that is especially valid for composites prepared from plate-like nanofillers. Besides the usually assumed exfoliated/intercalated morphology, i.e. individual platelets and tactoids, such nanocomposites often contain large particles, and a network structure developing at large extent of exfoliation. Aggregation and orientation are the most important structural phenomena in nanotube or nanofiber reinforced composites, and ag-gregation is a major problem also in composites prepared with spherical particles. The surface characteristics of nanofillers and interactions are rarely determined or known; the related problems are discussed in the paper in detail. The surface of these reinforcements is modified practically always. The goal of the modification is to improve dispersion and/or adhesion in nanotube and spherical particle reinforced composites, and to help exfoliation in nanocomposites containing platelets. However, modification decreases surface energy often leading to decreased interaction with the matrix. Very limited information exists about interphase formation and the properties of the interphase in nanocomposites, although they must influence properties considerably. The properties of nanocomposites are usually far from the expectations, the main reason being insufficient homogeneity, undefined structure and improper adhesion. In spite of considerable difficulties nanocomposites have great potentials especially in functional applications. Several nanocomposite products are already used in industrial practice demonstrated by a few examples in the article.


A randomized, double-blind, placebo-controlled trial on intravenous ibuprofen L-lysine for the early closure of nonsymptomatic patent ductus arteriosus within 72 hours of birth in extremely low-birth-weight infants.
A multicenter, double-blind, randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of intravenous (IV) ibuprofen (L-lysine) for the early closure of nonsymptomatic patent ductus arteriosus (PDA) within 72 hours of birth in extremely low-birth-weight (ELBW) infants with evidence of ductal shunting by echocardiogram. Eleven sites enrolled 136 infants with nonsymptomatic early PDA (gestational age < 30 weeks; body weight 500 to 1000 g) to receive a 3-day course (10 mg/kg, 5 mg/kg, and 5 mg/kg) of IV ibuprofen ( N = 68) or placebo ( N = 68). Cardiac echocardiogram was performed on study days 1 and 14, and with rescue. Infants were followed to 36 weeks postconceptional age. Patient demographics, mean (standard deviation), were similar between ibuprofen and placebo: birth weight: 798.5 g (128.7) versus 797.3 g (132.8); gestational age: 26.1 weeks (1.3) versus 26.2 weeks (1.4); and age at first dose: 1.5 days (0.7). The intent-to-treat analysis of the primary endpoint, subjects rescued, died, or dropped through study day 14, was 21/68 (30.9%) with ibuprofen and 36/68 (52.9%) for placebo ( P = 0.005). Death, intraventricular hemorrhage, necrotizing enterocolitis, daily fluid intake/output, liver function, bronchopulmonary dysplasia, and retinopathy of prematurity did not differ. A trend toward decreased periventricular leukomalacia by ibuprofen was noted. IV ibuprofen was effective and safe in the early closure of PDA in preterm neonates.


New specimens of Nemegtomaia from the Baruungoyot and Nemegt Formations (Late Cretaceous) of Mongolia.
Two new specimens of the oviraptorid theropod Nemegtomaia barsboldi from the Nemegt Basin of southern Mongolia are described. Specimen MPC-D 107/15 was collected from the upper beds of the Baruungoyot Formation (Campanian-Maastrichtian), and is a nest of eggs with the skeleton of the assumed parent of Nemegtomaia on top in brooding position. Much of the skeleton was damaged by colonies of dermestid coleopterans prior to its complete burial. However, diagnostic characters are recovered from the parts preserved, including the skull, partial forelimbs (including the left hand), legs, and distal portions of both feet. Nemegtomaia represents the fourth known genus of oviraptorid for which individuals have been found on nests of eggs. The second new specimen, MPC-D 107/16, was collected a few kilometers to the east in basal deposits of the Nemegt Formation, and includes both hands and femora of a smaller Nemegtomaia individual. The two formations and their diverse fossil assemblages have been considered to represent sequential time periods and different environments, but data presented here indicate partial overlap across the Baruungoyot-Nemegt transition. All other known oviraptorids from Mongolia and China are known exclusively from xeric or semi-arid environments. However, this study documents that Nemegtomaia is found in both arid/aeolian (Baruungoyot Formation) and more humid/fluvial (Nemegt Formation) facies.


Phylogenomic analyses of bat subordinal relationships based on transcriptome data.
Bats, order Chiroptera, are one of the largest monophyletic clades in mammals. Based on morphology and behaviour bats were once differentiated into two suborders Megachiroptera and Microchiroptera Recently, researchers proposed alternative views of chiropteran classification (suborders Yinpterochiroptera and Yangochiroptera) based on morphological, molecular and fossil evidence. Since genome-scale data can significantly increase the number of informative characters for analysis, transcriptome RNA-seq data for 12 bat taxa were generated in an attempt to resolve bat subordinal relationships at the genome level. Phylogenetic reconstructions were conducted using up to 1470 orthologous genes and 634,288 aligned sites. We found strong support for the Yinpterochiroptera-Yangochiroptera classification. Next, we built expression distance matrices for each species and reconstructed gene expression trees. The tree is highly consistent with sequence-based phylogeny. We also examined the influence of taxa sampling on the performance of phylogenetic methods, and found that the topology is robust to sampling. Relaxed molecular clock estimates the divergence between Yinpterochiroptera and Yangochiroptera around 63 million years ago. The most recent common ancestor of Yinpterochiroptera, corresponding to the split between Rhinolophoidea and Pteropodidae (Old World Fruit bats), is estimated to have occurred 60 million years ago. Our work provided a valuable resource to further explore the evolutionary relationship within bats.


Oral health status among Kenyans in a rural arid setting: dental caries experience and knowledge on its causes.
To determine the dental caries experience and knowledge on the causes and preventive measures for dental diseases. A community based cross-sectional descriptive study. Elwak sub-district hospital, North Eastern Province, Kenya. One hundred and forty one adults who presented themselves during a dental check up at a sub-district hospital and gave written consent. Dental caries status and knowledge on its causes and preventive measures. The importance of outreach programmes in obtaining information as well as helping to alleviate the pain and suffering caused by dental diseases among communities living in remote areas is also revealed. Of the one hundred and forty one individuals, who were included in the study, 63.1% were women and 36.9% were men. Their ages ranged between 18 and over 65 years. 41.1% were in the 18-24-year age bracket. Regarding the oral health knowledge, 43% did not know any causes of dental diseases while 36%, 17% and 12% knew that diet, "dirt" on teeth and bacteria were possible causes, respectively. Fifty percent did not know any preventive measures for dental diseases while the rest indicated abstention from the consumption of sugary foods; and only 0.8% mentioned use of fluoridated toothpaste as a preventive measure for dental caries. 56.7% of the subjects were caries free. The mean DMFT for all ages was 3.4. Of those with caries 72.1% were women. There is a low level of oral health awareness and a moderately high level of dental caries experience in this community with women apparently carrying the biggest burden of dental caries.


Relative letter-position coding revisited.
The notion that the brain achieves visual word recognition by encoding the relative positions of letters with open-bigram representations (e.g., 'h-e', 'h-r' and 'e-r' driving recognition of 'her') has been successful in accounting for many behaviors and phenomena. However, one characteristic of open-bigrams has remained unexplored: How is the activation of a bigram modulated by the distance between its constituents in the visual field? On the one hand, contiguous letters (e.g., 'at' in 'father') may allow for a clearer percept of the bigram. On the other hand, an increasing distance between letters (e.g., 'ae' in 'father') should create more certainty about their relative positions, which is precisely what the bigram is meant to convey. This matter was investigated with two experiments in which participants indicated whether target pairs of letters occurred in random letter strings. They were instructed that letter order mattered (i.e., 'a-b' does not occur in 'kbac'), while letter contiguity did not (i.e., 'a-b' occurs in 'akcb'). Controlling for crowding and eccentricity, bigrams were recognized faster upon decreasing the letter distance. However, when switching the target letter order (meaning the string should be met by a 'no' response), shorter letter distances yielded slower responses and more false positives. Neither relative position-coding models nor absolute position-coding models accommodate both these patterns at once. We discuss how a complete account of our effects may instead combine elements from both model types.


The Klebsiella pneumoniae ter Operon Enhances Stress Tolerance.
Healthcare-acquired infections are a leading cause of disease in patients that are hospitalized or in long-term-care facilities. Klebsiella pneumoniae (Kp) is a leading cause of bacteremia, pneumonia, and urinary tract infections in these settings. Previous studies have established that the ter operon, a genetic locus that confers tellurite oxide (K2TeO3) resistance, is associated with infection in colonized patients. Rather than enhancing fitness during infection, the ter operon increases Kp fitness during gut colonization; however, the biologically relevant function of this operon is unknown. First, using a murine model of urinary tract infection, we demonstrate a novel role for the ter operon protein TerC as a bladder fitness factor. To further characterize TerC, we explored a variety of functions, including resistance to metal-induced stress, resistance to radical oxygen species-induced stress, and growth on specific sugars, all of which were independent of TerC. Then, using well-defined experimental guidelines, we determined that TerC is necessary for tolerance to ofloxacin, polymyxin B, and cetylpyridinium chloride. We used an ordered transposon library constructed in a Kp strain lacking the ter operon to identify the genes that are required to resist K2TeO3-induced and polymyxin B-induced stress, which suggested that K2TeO3-induced stress is experienced at the bacterial cell envelope. Finally, we confirmed that K2TeO3 disrupts the Kp cell envelope, though these effects are independent of ter. Collectively, the results from these studies indicate a novel role for the ter operon as a stress tolerance factor, thereby explaining its role in enhancing fitness in the gut and bladder.


Viral hepatitis and pregnancy.
The management of viral hepatitis in the setting of pregnancy requires special consideration. There are five liver-specific viruses (hepatitis A, B, C, D, E), each with unique epidemiology, tendency to chronicity, risk of liver complications and response to antiviral therapies. In the setting of pregnancy, the liver health of the mother, the influence of pregnancy on the clinical course of the viral infection and the effect of the virus or liver disease on the developing infant must be considered. Although all hepatitis viruses can harm the mother and the child, the greatest risk to maternal health and subsequently the fetus is seen with acute hepatitis A virus or hepatitis E virus infection during pregnancy. By contrast, the primary risks for hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus are related to the severity of the underlying liver disease in the mother and the risk of mother-to-child transmission (MTCT) for HBV and HCV. The prevention of MTCT is key to reducing the global burden of chronic viral hepatitis, and prevention strategies must take into consideration local health-care and socioeconomic challenges. This Review presents the epidemiology of acute and chronic viral hepatitis infection in pregnancy, the effect of pregnancy on the course of viral infection and, conversely, the influence of the viral infection on maternal and infant outcomes, including MTCT.


Models for Golgi traffic: a critical assessment.
A variety of secretory cargoes move through the Golgi, but the pathways and mechanisms of this traffic are still being debated. Here, we evaluate the strengths and weaknesses of five current models for Golgi traffic: (1) anterograde vesicular transport between stable compartments, (2) cisternal progression/maturation, (3) cisternal progression/maturation with heterotypic tubular transport, (4) rapid partitioning in a mixed Golgi, and (5) stable compartments as cisternal progenitors. Each model is assessed for its ability to explain a set of key observations encompassing multiple cell types. No single model can easily explain all of the observations from diverse organisms. However, we propose that cisternal progression/maturation is the best candidate for a conserved core mechanism of Golgi traffic, and that some cells elaborate this core mechanism by means of heterotypic tubular transport between cisternae.