A H2S-Triggered Dual-Modal Second Near-Infrared/Photoacoustic Intelligent Nanoprobe for Highly Specific Imaging of Colorectal Cancer.
An endogenous H2S-triggered intelligent optical nanoprobe combining second near-infrared (NIR-II) fluorescence with photoacoustic (PA) imaging can provide more comprehensive information to further improve the sensitivity and reliability of diagnosis for colorectal tumor, which is rarely explored. Herein, an endogenous H2S-triggered SiO2@Ag nanoprobe was designed for in situ dual-modal NIR-II/PA imaging of colorectal cancer. The designed dual-modal nanoprobe can be converted to SiO2@Ag2S after in situ biosynthesis via a sulfuration reaction with the over-expressed endogenous H2S in the colorectal tumor. More importantly, the designed SiO2@Ag nanoprobe exhibits high sensitivity and specificity for diagnosing colorectal cancer in vivo via dual-modal NIR-II/PA imaging. These results provide a new NIR-II/PA dual-modal imaging strategy for noninvasive intelligent detection of colorectal cancer.


Structural basis for DNA strand separation by a hexameric replicative helicase.
Hexameric helicases are processive DNA unwinding machines but how they engage with a replication fork during unwinding is unknown. Using electron microscopy and single particle analysis we determined structures of the intact hexameric helicase E1 from papillomavirus and two complexes of E1 bound to a DNA replication fork end-labelled with protein tags. By labelling a DNA replication fork with streptavidin (dsDNA end) and Fab (5' ssDNA) we located the positions of these labels on the helicase surface, showing that at least 10 bp of dsDNA enter the E1 helicase via a side tunnel. In the currently accepted 'steric exclusion' model for dsDNA unwinding, the active 3' ssDNA strand is pulled through a central tunnel of the helicase motor domain as the dsDNA strands are wedged apart outside the protein assembly. Our structural observations together with nuclease footprinting assays indicate otherwise: strand separation is taking place inside E1 in a chamber above the helicase domain and the 5' passive ssDNA strands exits the assembly through a separate tunnel opposite to the dsDNA entry point. Our data therefore suggest an alternative to the current general model for DNA unwinding by hexameric helicases.


Assessing the cultural competence of oral health research conducted with migrant children.
Traditional assessment of research quality addresses aspects of scientific rigor, however, ensuring barriers to participation by people of different cultural backgrounds are addressed requires cultural competence. The aim of this research was to assess the cultural competence of oral health research conducted with migrant children. A protocol was developed with explicit inclusion and exclusion criteria. Electronic databases were searched from 1995 to 2009. Each study was assessed for cultural competence using the assessment criteria and a template developed as a proof-of-concept approach. Of the 2059 articles identified, 58 met inclusion criteria (n = 48 studies). There were four (8.3%) cohort studies, five (10.4%) intervention studies, 37 (77.1%) quantitative cross-sectional studies, and two (4.2%) were qualitative studies. Overall, migrant children had worse oral health outcomes in all studies compared with their host-country counterparts. All studies rated poorly in the cultural competence assessment. Appropriate inclusion of all potentially vulnerable groups in research will result in better estimates and understandings of oral health, and more reliable recommendations for prevention and management.


Urease activity of enterobacteriaceae: which medium to choose.
Detection and intensity of urease activity in enterobacteriaceae greatly varies as a function of the media or techniques used, or both. A comparative investigation on several solid and liquid media led us to the following conclusions. (i) Detection of Proteus spp. can be adequately performed with the highly selective solid medium described by Cook (1948), as well as with the different liquid media described (Stuart standard and rapid media; Elek medium). (ii) Detection of Klebsiella should be based upon urease production on solid media with low buffer capacity (Christensen, 1946). (iii) For the identification of Yersinia, either the solid Christensen urea agar or the rapid Elek technique give optimal results.


Clandestinovirus: A Giant Virus With Chromatin Proteins and a Potential to Manipulate the Cell Cycle of Its Host Vermamoeba vermiformis.
For several decades, the vast world of DNA viruses has been expanding constantly. Various discoveries in this field have broadened our knowledge and revealed that DNA viruses encode many functional features, which were once thought to be exclusive to cellular life. Here, we report the isolation of a giant virus named "clandestinovirus," grown on the amoebal host Vermamoeba vermiformis. This virus was discovered in a mixed co-culture associated with another giant virus, Faustovirus ST1. Clandestinovirus possesses a linear dsDNA genome of 581,987 base pairs containing 617 genes. Phylogenetically, clandestinovirus is most closely related to Acanthamoeba castellanii medusavirus and was considered a member of the proposed Medusaviridae family. However, clandestinovirus genome is 65% larger than that of medusavirus, emphasizing the considerable genome size variation within this virus family. Functional annotation of the clandestinovirus genes suggests that the virus encodes four core histones. Furthermore, clandestinovirus appears to orchestrate the cell cycle and mitochondrial activities of the infected host by virtue of encoding a panel of protein kinases and phosphatases, and a suite of functionally diverse mitochondrial protein homologs, respectively. Collectively, these observations illuminate a strategy employed by clandestinovirus to optimize the intracellular environment for efficient virus propagation.


Long-term cognitive functional limitations post stroke: objective assessment compared with self-evaluations and spouse reports.
This study was part of a Swedish interdisciplinary research project targeting accessibility problems in public transport for people with cognitive functional limitations (CFLs). The objective was to describe and compare different assessment perspectives of long-term CFLs among community citizens having had CFLs in the acute stroke phase but with moderate physical limitations. Eighty-four participants in ordinary housing 18-36 months post stroke, initially sampled from a national quality stroke register, received data collection home-visits. The Cognistat screening instrument was used for an objective assessment, and a study-specific questionnaire for self-evaluations of CFLs. A revised form of the latter questionnaire was used for reports from spouses of a subset of 30 participants. The agreement between self-evaluated CFLs and spouse reports was analysed by percentage agreement and Cohen's kappa, whereas differences in ratings were tested by McNemar's test, as were differences between objective and self-evaluated/spouse-reported occurrence of CFLs. Regardless of the different perspectives applied, CFLs were frequent. In absence of significant difference in ratings, the percentage agreement between self-evaluations and spouse reports was good or very good, whereas kappa values were less encouraging. Overall, participants and spouses expressed more CFLs, as compared with the screening. Most consistency was demonstrated for the area of calculation. When researchers and clinicians solely rely on cognitive screenings in their investigations, there is a considerable risk for underestimations of CFLs.


Police responses to persons with mental illness: does the label matter?
With the movement of persons with mental illness out of hospitals and into the community, the frequency of contact between police officers and such persons, in crisis or otherwise, has increased significantly. How police respond in these situations has important consequences for the subject, police officers, and the community. Officers (n = 554) from police departments in a major metropolitan area participated in a vignette experiment that examined how information that a subject has a mental illness influences the way police officers respond in several types of situations. Results indicate that officers are less likely to take action based on information provided by victims and witnesses with mental illness. No differences were found in response to suspects with or without a mental illness. The effects of officer characteristics and perceptions of the subject on responses to the vignettes were also examined. Findings suggest several directions for training and future research.


An improved taxonomic sampling is a necessary but not sufficient condition for resolving inter-families relationships in Caridean decapods.
During the past decade, a large number of multi-gene analyses aimed at resolving the phylogenetic relationships within Decapoda. However relationships among families, and even among sub-families, remain poorly defined. Most analyses used an incomplete and opportunistic sampling of species, but also an incomplete and opportunistic gene selection among those available for Decapoda. Here we test in the Caridea if improving the taxonomic coverage following the hierarchical scheme of the classification, as it is currently accepted, provides a better phylogenetic resolution for the inter-families relationships. The rich collections of the Muséum National d'Histoire Naturelle de Paris are used for sampling as far as possible at least two species of two different genera for each family or subfamily. All potential markers are tested over this sampling. For some coding genes the amplification success varies greatly among taxa and the phylogenetic signal is highly saturated. This result probably explains the taxon-heterogeneity among previously published studies. The analysis is thus restricted to the genes homogeneously amplified over the whole sampling. Thanks to the taxonomic sampling scheme the monophyly of most families is confirmed. However the genes commonly used in Decapoda appear non-adapted for clarifying inter-families relationships, which remain poorly resolved. Genome-wide analyses, like transcriptome-based exon capture facilitated by the new generation sequencing methods might provide a sounder approach to resolve deep and rapid radiations like the Caridea.


Northern peatland initiation lagged abrupt increases in deglacial atmospheric CH4.
Peatlands are a key component of the global carbon cycle. Chronologies of peatland initiation are typically based on compiled basal peat radiocarbon (14C) dates and frequency histograms of binned calibrated age ranges. However, such compilations are problematic because poor quality 14C dates are commonly included and because frequency histograms of binned age ranges introduce chronological artefacts that bias the record of peatland initiation. Using a published compilation of 274 basal 14C dates from Alaska as a case study, we show that nearly half the 14C dates are inappropriate for reconstructing peatland initiation, and that the temporal structure of peatland initiation is sensitive to sampling biases and treatment of calibrated 14C dates. We present revised chronologies of peatland initiation for Alaska and the circumpolar Arctic based on summed probability distributions of calibrated 14C dates. These revised chronologies reveal that northern peatland initiation lagged abrupt increases in atmospheric CH4 concentration at the start of the Bølling-Allerød interstadial (Termination 1A) and the end of the Younger Dryas chronozone (Termination 1B), suggesting that northern peatlands were not the primary drivers of the rapid increases in atmospheric CH4. Our results demonstrate that subtle methodological changes in the synthesis of basal 14C ages lead to substantially different interpretations of temporal trends in peatland initiation, with direct implications for the role of peatlands in the global carbon cycle.


Autophagy Controls Acquisition of Aging Features in Macrophages.
Macrophages provide a bridge linking innate and adaptive immunity. An increased frequency of macrophages and other myeloid cells paired with excessive cytokine production is commonly seen in the aging immune system, known as 'inflamm-aging'. It is presently unclear how healthy macrophages are maintained throughout life and what connects inflammation with myeloid dysfunction during aging. Autophagy, an intracellular degradation mechanism, has known links with aging and lifespan extension. Here, we show for the first time that autophagy regulates the acquisition of major aging features in macrophages. In the absence of the essential autophagy gene Atg7, macrophage populations are increased and key functions such as phagocytosis and nitrite burst are reduced, while the inflammatory cytokine response is significantly increased - a phenotype also observed in aged macrophages. Furthermore, reduced autophagy decreases surface antigen expression and skews macrophage metabolism toward glycolysis. We show that macrophages from aged mice exhibit significantly reduced autophagic flux compared to young mice. These data demonstrate that autophagy plays a critical role in the maintenance of macrophage homeostasis and function, regulating inflammation and metabolism and thereby preventing immunosenescence. Thus, autophagy modulation may prevent excess inflammation and preserve macrophage function during aging, improving immune responses and reducing the morbidity and mortality associated with inflamm-aging.


Caring for cancer patients with an intellectual disability: Attitudes and care perceptions of UK oncology nurses.
Caring for people with cancer or an intellectual disability (ID) is stressful: little is known about the combined impact of caring for cancer patients with an ID, though this is expected to be especially challenging. Eighty-three nurses, working in oncology or a related field (i.e. palliative care) were recruited. Perceptions of caring for patients with and without an ID were measured, alongside potentially confounding information about participant demographic characteristics and perceived stress. Participants felt less comfortable communicating with patients with an ID about their illness (F(1,82) = 59.52, p < 0.001), more reliant on a caregiver for communication (F(1,82) = 26.29, p < 0.001), and less confident that the patient's needs would be identified (F(1,82) = 42.03, p < 0.001) and met (F(1,81) = 62.90, p < 0.001). Participants also believed that caring for this patient group would induce more stress, compared with patients without an ID (F(1,81) = 31.592, p < 0.001). Previous experience working with ID patient groups appears to mitigate some perceptions about providing care to this population. Caring for cancer patients with an ID may intensify this, already difficult, role. Through training and knowledge exchange, oncology nurse's confidence in communication, providing appropriate care, and positivity towards this patient group may be improved.


Human liver thermostable phenol sulfotransferase: photoaffinity labeling with 2-iodo-4-azidophenol.
Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of phenolic drugs, neurotransmitters, and xenobiotic compounds. Human tissues contain at least two forms of PST, which differ in their substrate specificities, inhibitor sensitivities, physical properties, and regulation. One form of the enzyme is thermostable (TS) and catalyzes the sulfate conjugation of micromolar concentrations of "simple" phenols. The other form of PST is thermolabile and catalyzes the sulfate conjugation of micromolar concentrations of dopamine and other phenolic monoamines. Quantitative structure-activity relationship (QSAR) analyses of substrate kinetic data obtained with purified human liver TS PST made it possible to design a photoreactive substrate for this form of the enzyme. Because of the very high affinity of TS PST for 2-halogenated phenols, 2-iodo-4-azidophenol (IAP) was synthesized and tested for this purpose. The Km predicted for IAP on the basis of QSAR analysis was 95 nM. The apparent Km determined experimentally was 52 nM. UV irradiation of partially purified human liver TS PST in the presence of [125 I]IAP and 3'-phosphoadenosine-5'-phosphosulfate, the sulfate donor for the reaction, resulted in the radioactive labeling of two proteins, with molecular weights of 32,000 and 34,000, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Inhibitors of the reaction catalyzed by TS PST, including 2,6-dichloro-4-nitrophenol-3'-phosphoadenosine- 5'-phosphate and NaCl, as well as 2-iodophenol, a competing substrate, inhibited the photolabeling of both of these proteins by [125I]IAP in a concentration-dependent fashion. Partially purified TS PST was then radioactively labeled with [125]IAP and was subjected to gel filtration high performance liquid chromatography to verify that the photo-affinity-labeled proteins detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coeluted with TS PST enzyme activity. Photoaffinity labeling of TS PST will be useful in studies of the molecular characteristics of the protein and its active site, as well as in the purification of this important drug-metabolizing enzyme.


Using the INDEPTH HDSS to build capacity for chronic non-communicable disease risk factor surveillance in low and middle-income countries.
Chronic non-communicable diseases (NCDs) are the leading cause of morbidity, mortality, and disability worldwide. More than 80% of chronic disease deaths occur in low-income and middle-income countries. Epidemiological data on the burden of chronic NCD and the risk factors which predict them are lacking in most low-income countries. The INDEPTH Network (http://www.indepth-network.org) which includes the Health and Demographic Surveillance System (HDSS) with many surveillance sites in low-middle income countries provided an opportunity to establish surveillance of the major chronic NCD risk factors in 2005 using a standardised approach. This paper presents the conceptual framework and research design of the chronic NCD risk factor surveillance within nine rural INDEPTH HDSS settings in Asia. This multi-site study was designed as a baseline cross-sectional survey with sufficient sample size to measure trends over time. In each of nine HDSS sites in five Asian countries, a sample of 2,000 men and women aged 25-64 years, using the WHO STEPwise approach to Surveillance (http://who.int/chp/steps), was selected using stratified random sampling (in each 10-year interval) from the HDSS sampling frame. A total of 18,494 men and women from the nine sites were interviewed with an overall response rate of 98%. The major NCDs risk factors included self-reported information on tobacco and alcohol consumption, fruit and vegetable intake, physical activity patterns, and measured body weight, height, waist circumference, and blood pressure. A series of training sessions were conducted for research scientists, supervisors, and surveyors in each site. Data quality was ensured through spot check, re-check, and data validation procedures, including accuracy and completeness of data obtained. Standardised data entry programme, created using the EPIDATA software, was used to ensure uniform database structure across sites. The data merging and analysis were done using STATA Version 10. This multi-site study confirmed the feasibility of conducting chronic NCD risk factor surveillance in the low and middle-income settings by integrating the chronic NCDs risk factor surveillance into an existing HDSS data collection and management setting. This collaborative work has provided reliable epidemiological data as a basis for developing chronic NCD prevention and control activities.


Inappropriate cathepsin K secretion promotes its enzymatic activation driving heart and valve malformation.
Although congenital heart defects (CHDs) represent the most common birth defect, a comprehensive understanding of disease etiology remains unknown. This is further complicated since CHDs can occur in isolation or as a feature of another disorder. Analyzing disorders with associated CHDs provides a powerful platform to identify primary pathogenic mechanisms driving disease. Aberrant localization and expression of cathepsin proteases can perpetuate later-stage heart diseases, but their contribution toward CHDs is unclear. To investigate the contribution of cathepsins during cardiovascular development and congenital disease, we analyzed the pathogenesis of cardiac defects in zebrafish models of the lysosomal storage disorder mucolipidosis II (MLII). MLII is caused by mutations in the GlcNAc-1-phosphotransferase enzyme (Gnptab) that disrupt carbohydrate-dependent sorting of lysosomal enzymes. Without Gnptab, lysosomal hydrolases, including cathepsin proteases, are inappropriately secreted. Analyses of heart development in gnptab-deficient zebrafish show cathepsin K secretion increases its activity, disrupts TGF-β-related signaling, and alters myocardial and valvular formation. Importantly, cathepsin K inhibition restored normal heart and valve development in MLII embryos. Collectively, these data identify mislocalized cathepsin K as an initiator of cardiac disease in this lysosomal disorder and establish cathepsin inhibition as a viable therapeutic strategy.


Chromatin and beyond: the multitasking roles for SIRT6.
In recent years there has been a large expansion in our understanding of SIRT6 biology including its structure, regulation, biochemical activity, and biological roles. SIRT6 functions as an ADP-ribosylase and NAD(+)-dependent deacylase of both acetyl groups and long-chain fatty-acyl groups. Through these functions SIRT6 impacts upon cellular homeostasis by regulating DNA repair, telomere maintenance, and glucose and lipid metabolism, thus affecting diseases such diabetes, obesity, heart disease, and cancer. Such roles may contribute to the overall longevity and health of the organism. Until recently, the known functions of SIRT6 were largely restricted to the chromatin. In this article we seek to describe and expand this knowledge with recent advances in understanding the mechanisms of SIRT6 action and their implications for human biology and disease.


Retrieving functional pathways of biomolecules from single-particle snapshots.
A primary reason for the intense interest in structural biology is the fact that knowledge of structure can elucidate macromolecular functions in living organisms. Sustained effort has resulted in an impressive arsenal of tools for determining the static structures. But under physiological conditions, macromolecules undergo continuous conformational changes, a subset of which are functionally important. Techniques for capturing the continuous conformational changes underlying function are essential for further progress. Here, we present chemically-detailed conformational movies of biological function, extracted data-analytically from experimental single-particle cryo-electron microscopy (cryo-EM) snapshots of ryanodine receptor type 1 (RyR1), a calcium-activated calcium channel engaged in the binding of ligands. The functional motions differ substantially from those inferred from static structures in the nature of conformationally active structural domains, the sequence and extent of conformational motions, and the way allosteric signals are transduced within and between domains. Our approach highlights the importance of combining experiment, advanced data analysis, and molecular simulations.


Comparison of a novel insulin bolus-patch with pen/syringe injection to deliver mealtime insulin for efficacy, preference, and quality of life in adults with diabetes: a randomized, crossover, multicenter study.
This study compared the efficacy, safety, device satisfaction, and quality of life (QOL) in people with diabetes using an insulin bolus-patch versus current devices (pen/syringe) to deliver mealtime insulin. Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2) were randomized to bolus-patch or current injection device (55% pen and 45% syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study. Efficacy was assessed by equivalence in mean daily seven-point blood glucose (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device effects (ADEs), and adverse events (AEs). Device satisfaction was determined by the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the validated Diabetes Specific QOL Scale (DSQOLS). Using bolus-patch, MDBG (mean±SE) was equivalent to that using pen/syringe (8.61±0.28 vs. 9.02±0.26 mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower using bolus-patch (3.18±0.18 vs. 3.63±0.17 mmol/L; P=0.004), as was the coefficient of variation (CV) (37.2±1.7 vs. 40.3±1.7%; P=0.046). Hemoglobin A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between groups. There were no severe hypoglycemia episodes or serious ADEs. Between-device AEs were comparable. Subjects scored better on six of seven subscales on the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus pen/syringe. At study completion, 76% of subjects would choose to switch to bolus-patch (P=0.001). Delivery of mealtime insulin with bolus-patch compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven-point blood glucose measurements, good safety, significant device satisfaction, and improved QOL.


Cellular immune responses in peripheral blood lymphocytes of Giardia infected squirrel monkey (Saimiri boliviensis boliviensis) treated with Fenbendazole.
Cellular immune responses were tested to determine the effect of fenbendazole on the function of lymphocytes from Bolivian squirrel monkeys (Samiri boliviensis boliviensis). Giardia-infected squirrel monkeys were treated with commercially available fenbendazole (FBZ)-medicated monkey chow. Immune responses were compared between historical controls (Giardia naïve, untreated with FBZ (control animals)) and Giardia-infected, FBZ-treated squirrel monkeys (study animals). Peripheral blood lymphocytes from study monkeys had significantly lower stimulation indices compared to control animals when cultured in vitro with concanavalin A (Con A) (p<0.0001), phytohaemagglutinin (PHA) (p<0.0001) and lipopolysaccharide (LPS) (p<0.0001). PBMCs were also analyzed for IFN-γ producing cells in response to stimulation with Con A, PHA, PWM, and LPS by the cytokine ELISPOT assay. Significantly higher responses to Con A- (p<0.0001), and PHA- (p<0.001) stimulated cultures from Giardia-infected and fenbendazole treated compared to controls. Flow cytometric analysis for expression of cell surface markers revealed a significant increase in B- and NKT-lymphocytes and significant decrease in CD14+CD16+ monocytes after FBZ treatment. Also, circulating plasma cytokines IFN-γ, TNF-α, IL-12p40, IL-1β, IL-10, IL-13, IL-1ra, IL-6 and IL-4 were significantly decreased after FBZ treatment. Comparison of hematologic parameters between controls and FBZ-treated squirrel monkeys revealed significantly lower numbers of total leukocytes, neutrophils, monocytes, and eosinophils compared to controls. However, erythrocyte indices (red cell count, hemoglobin and hematocrit were significantly higher in FBZ-treated monkeys. Our findings suggest that fenbendazole treatment may alter sensitive immune and molecular measures of inflammation. Postponing the experimental use of squirrel monkeys until at least 6 weeks after FBZ treatment should be considered.


Comparison of Methods for Estimating Unbound Intracellular-to-Medium Concentration Ratios in Rat and Human Hepatocytes Using Statins.
It is essential to estimate concentrations of unbound drugs inside the hepatocytes to predict hepatic clearance, efficacy, and toxicity of the drugs. The present study was undertaken to compare predictability of the unbound hepatocyte-to-medium concentration ratios (Kp,uu) by two methods based on the steady-state cell-to-medium total concentration ratios at 37°C and on ice (Kp,uu,ss) and based on their initial uptake rates (Kp,uu,V0). Poorly metabolized statins were used as test drugs because of their concentrative uptake via organic anion-transporting polypeptides. Kp,uu,ss values of these statins provided less interexperimental variation than the Kp,uu,V0 values, because only data at longer time are required for Kp,uu,ss Kp,uu,V0 values for pitavastatin, rosuvastatin, and pravastatin were 1.2- to 5.1-fold Kp,uu,ss in rat hepatocytes; Kp,uu,V0 values in human hepatocytes also tended to be larger than corresponding Kp,uu,ss To explain these discrepancies, theoretical values of Kp,uu,ss and Kp,uu,V0 were compared with true Kp,uu (Kp,uu,true), considering the inside-negative membrane potential and ionization of the drugs in hepatocytes and medium. Membrane potentials were approximately -30 mV in human hepatocytes at 37°C and almost abolished on ice. Theoretical equations considering the membrane potentials indicate that Kp,uu,ss values for the statins are 0.85- to 1.2-fold Kp,uu,true, whereas Kp,uu,V0 values are 2.2- to 3.1-fold Kp,uu,true, depending on the ratio of the passive permeability of the ionized to nonionized forms. In conclusion, Kp,uu,ss values of anions are similar to Kp,uu,true when the inside-negative membrane potential is considered. This suggests that Kp,uu,ss is preferable for estimating the concentration of unbound drugs inside the hepatocytes.


Paper-based electrochemiluminescence sensor for highly sensitive detection of amyloid-β oligomerization: Toward potential diagnosis of Alzheimer's disease.
Development of a rapid and sensitive method for Aβ(1-42) aggregation detection is of great importance to overcome the limitations of conventional techniques. In this study, we developed a label-free paper-based electrochemiluminescence sensor for amyloid-β aggregation detection toward potential diagnosis of Alzheimer's disease (AD). The paper-based chip used in the system serves as a low-cost and disposable detection method. In this detection platform, the bonding of [Ru(phen)2dppz]2+ to Aβ(1-42) aggregates results in enhanced electrochemiluminescence due to the change in the polarity of the microenvironment when [Ru(phen)2dppz]2+ intercalated into the β-sheets during oligomerization. The oligomerization process of Aβ(1-42) can be monitored in real time by the novel method, and as low as 100 pM equivalent monomer concentration of Aβ(1-42) could be detected simultaneously. In addition, the cerebrospinal fluid of transgenic AD model mice was tested by this method, which is highly consistent with genetic identification. In addition, we demonstrated that this detection platform could be a potential new method for the screening of Aβ(1-42) aggregation inhibitors, highlighting the practical application capacity of this platform. The platform is label free, low cost and sensitive. Therefore, the proposed platform holds great promise for the diagnosis of AD.


Long-distance practical quantum key distribution by entanglement swapping.
We develop a model for practical, entanglement-based long-distance quantum key distribution employing entanglement swapping as a key building block. Relying only on existing off-the-shelf technology, we show how to optimize resources so as to maximize secret key distribution rates. The tools comprise lossy transmission links, such as telecom optical fibers or free space, parametric down-conversion sources of entangled photon pairs, and threshold detectors that are inefficient and have dark counts. Our analysis provides the optimal trade-off between detector efficiency and dark counts, which are usually competing, as well as the optimal source brightness that maximizes the secret key rate for specified distances (i.e. loss) between sender and receiver.


Adult lymphoblastic lymphoma in Taiwan: an analysis of treatment results of 26 patients.
Lymphoblastic lymphoma (LBL) frequently affects young adults and usually presents with a mediastinal mass as well as bone marrow involvement. Although the frequency of LBL in the Far East is higher than that of Western countries, no reports regarding treatment of this disease have as yet been reported. We herein report our treatment experience and verify the efficacy of the Stanford/Northern California Oncology Group (NCOG) protocol for this disease and recommend treatment strategies for LBL patients. We retrospectively reviewed the medical records of adult LBL patients treated in our hospital from 1986 to 1996. Twenty-seven patients were diagnosed to have LBL. These patients' ages ranged from 17 to 73 years old with a median of 23. Nineteen patients had an initial stage IV disease. Of the 23 cases in which immunological studies were performed, 20 proved to be of T cell lineage, 1 of B cell type, and the other 2 lacked both T and B markers. Three major chemotherapeutic regimens including prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide-mechlorethamine, vincristine, procarbazine, prednisone (ProMACE-MOPP), cyclophosphamide, hydroxydaunomycin, vincristine, prednisone (CHOP), and the Stanford/NCOG protocol were used to treat 3, 6, and 15 patients, respectively. Two other patients were treated with two different chemotherapeutic regimens, respectively. One patient was excluded for analysis because of initial treatment by surgery. The complete response (CR) rates with ProMACE-MOPP, CHOP, and the Stanford/NCOG regimens were 0%, 17%, 80% and median overall survival 9, 8.5, and 15 months, respectively. Five patients with stage II-III diseases achieved long-term disease-free survival of 11-36 months with the Stanford/NCOG protocol with a median follow-up of 24 months. Four patients in late stage or relapse received allogeneic bone marrow transplantation (BMT). Two of them obtained long-term disease-free survival. Two other patients in CR were treated with high-dose chemotherapy (HDCT) supported with autologous BMT and peripheral blood stem cell transplantation (PBSCT), respectively. The patient receiving HDCT with autologous PBSCT died of LBL relapse 6 months after transplantation. The other patient undergoing HDCT with autologous BMT died of fulminant hepatitis 5.5 months after transplantation. The median overall survival of all these 26 patients was 12 months. B symptoms and treatment without the Stanford/NCOG protocol were found to have significantly negative impacts on both patients' overall and progression-free survivals. Our results suggest that the Stanford/NCOG protocol may be an effective chemotherapy for adult LBL and may provide long-term remission for patients in an early stage of disease. For those patients with LBL in an advanced stage or in relapse, HDCT with allogeneic or autologous BMT is probably the treatment of choice.


Induction, Subculture Cycle, and Regeneration of Callus in Safed Musli (Chlorophytum borivilianum) using Different Types of Phytohormones.
Chlorophytum borivilianum is an industrially valued medicinal crop. Propagation through seeds is not feasible because of low germination percentage and long dormancy period. Therefore, callus culture and plant regeneration can be an alternative to improve this crop production. Also, callus can serve as an alternative source of bioactive compounds. To evaluate the effect of different phytohormones on callus induction, subculture cycle, and regeneration studies of callus in C. borivilianum. Young shoot buds of C. borivilianum were inoculated on Murashige and Skoog medium fortified with 3% sucrose and different concentrations (0, 1, 5, 10, and 15 mg/L) of either naphthalene acetic acid or 2,4-dichlorophenoxyacetic acid or indole-3-acetic acid and callus induction was evaluated up to four subcultures cycles. Shoot regeneration from callus was studied on Murashige and Skoog media fortified with 6-benzylaminopurine andkinetin or thidiazuron at varied levels (0, 0.5, 1, 2, and 3 mg/L). Microshoots were rooted on Murashige and Skoog media supplemented with 1.0 mg/L indole-3-butyric acid and plantlets were acclimatized before transferred to the natural conditions. Callus induction was better evidenced on Murashige and Skoog media containing 5 mg/L 2,4-dichlorophenoxyacetic acid up to fourth subculture. Callus differentiated into shoots on Murashige and Skoog media fortified with 6-benzylaminopurine or kinetin, whereas thidiazuron completely failed to regenerate shoots. Furthermore, microshoots rooted on 1.0 mg/L indole-3-butyric acid containing Murashige and Skoog media. The rooted plantlets were successfully acclimatized and established in soil with 88.3% survivability. The type of auxins played an important role in inducing callus tissue from shoot bud explants of Safed musli. In future, this in vitro protocol could benefit in crop improvement programs and serve as a new source of bioactive compounds from Safed musli callus tissue for various therapeutic applications. Explants de-differentiated to form callus on Murashige and Skoog media containing 5 mg/L 2,4-D up to fourth subculture.Callus re-differentiated into shoots on Murashige and Skoog media fortified with 0.5 mg/L BAP.In vitro rooting of shoots was achieved on 1.0 mg/L IBA containing Murashige and Skoog media.The rooted plantlets were successfully acclimatized and established in soil with 88.3% survivability. Abbreviations used: MS: Murashige and Skoog, NAA: naphthalene acetic acid, 2,4-D: 2,4-dichlorophenoxyacetic acid, IAA: indole-3-acetic acid, BAP: 6-benzylaminopurine, Kn: Kinetin, TDZ: thidiazuron, IBA: indole-3-butyric acid, RCBD: Randomized Complete Block Design, DMRT: Duncan's Multiple Range Test.


Changes in functional performance measures in adults undergoing chemoradiation for primary malignant glioma: a feasibility study.
To investigate the feasibility of longitudinal assessment of functional performance measures in newly diagnosed postsurgical malignant glioma patients. Patients with histologically confirmed, clinically stable, postsurgical, and previously untreated high-grade glioma (HGG) or low-grade glioma (LGG) were studied. Using a prospective design, all participants performed a cardiopulmonary exercise test with expired gas analysis to assess cardiorespiratory function (VO(2peak)) immediately following surgical resection (mean, 10 days). Additional functional outcomes were skeletal muscle cross-sectional area (CSA) via magnetic resonance imaging, isokinetic muscle strength (isokinetic dynamometry), and body composition (air displacement plethysmography). Quality of life (QOL) was assessed by the Functional Assessment of Cancer Therapy-Brain scale. All study assessments were repeated at 6 and 24 weeks following surgery. Thirty-five patients (HGG, n = 25; LGG, n = 10) completed baseline assessments. Of these, 20 HGG (80%) and nine LGG (90%) and 15 HGG (60%) and nine LGG (90%) patients completed study assessments at 6 weeks and 24 weeks, respectively. Intention-to-treat analyses indicated several significant time-by-group interactions, with favorable improvements in functional and QOL endpoints from baseline to 24 weeks in the LGG cohort and unfavorable changes in the HGG cohort. Per-protocol analyses including participants assessed at all three study timepoints indicated significant improvements in VO(2peak) and fatigue from baseline to 24 weeks in the HGG cohort; peak workload, body composition, and muscle strength improved from baseline to 6 weeks (all p-values < .05). Longitudinal quantitative functional assessments are safe and feasible among select patients undergoing chemoradiation for primary malignant glioma. Large prospective studies investigating the clinical importance of these measures appear warranted.


Object Properties Influence Visual Guidance of Motor Actions.
The dynamic nature of the real world poses challenges for predicting where best to allocate gaze during object interactions. The same object may require different visual guidance depending on its current or upcoming state. Here, we explore how object properties (the material and shape of objects) and object state (whether it is full of liquid, or to be set down in a crowded location) influence visual supervision while setting objects down, which is an element of object interaction that has been relatively neglected in the literature. In a liquid pouring task, we asked participants to move empty glasses to a filling station; to leave them empty, half fill, or completely fill them with water; and then move them again to a tray. During the first putdown (when the glasses were all empty), visual guidance was determined only by the type of glass being set down-with more unwieldy champagne flutes being more likely to be guided than other types of glasses. However, when the glasses were then filled, glass type no longer mattered, with the material and fill level predicting whether the glasses were set down with visual supervision: full, glass material containers were more likely to be guided than empty, plastic ones. The key finding from this research is that the visual system responds flexibly to dynamic changes in object properties, likely based on predictions of risk associated with setting-down the object unsupervised by vision. The factors that govern these mechanisms can vary within the same object as it changes state.


The nature and correlates of change in depressive symptoms with cancer diagnosis: reaction and adaptation.
Major life events trigger change processes in mental health. We examined how depressive symptoms change in conjunction with cancer diagnosis during adulthood and old age, and whether sociodemographic variables, cognitive and health resources, and cancer-specific mortality risks moderate event-related reaction and adaptation. Specifically, we applied multiphase growth models to prospective longitudinal data from 2,848 participants (age at diagnosis: M = 69, SD = 9.91; 46% women) in the Health and Retirement Study (HRS) who reported receiving a cancer diagnosis while enrolled in the study. On average, individuals experienced a significant increase in depressive symptoms within 2 years of cancer diagnosis, still-elevated levels 2 years postdiagnosis, and smaller increases in depressive symptoms postdiagnosis relative to the increases observed prediagnosis. Better memory and lower cancer-specific mortality risks were protective against increases in depressive symptoms within 2 years of diagnosis and were associated with reporting fewer depressive symptoms 2 years postdiagnosis. Findings suggest that diagnosis-related changes in depressive symptoms are typically characterized by a multiphase pattern, but tremendous between-person differences also emerged within each phase. Follow-up analyses comparing a matched group (N = 2,272) who did not experience cancer provided an additional layer of evidence supporting our inferences. Results indicate that, on average, people adapt and adjust to the challenges accompanying a cancer diagnosis, and illustrate the utility of using natural experiments such as major life events as a paradigm for studying developmental change processes.


Notch signalling is required for cyclic expression of the hairy-like gene HES1 in the presomitic mesoderm.
Somitic segmentation provides the framework on which the segmental pattern of the vertebrae, some muscles and the peripheral nervous system is established. Recent evidence indicates that a molecular oscillator, the 'segmentation clock', operates in the presomitic mesoderm (PSM) to direct periodic expression of c-hairy1 and lunatic fringe (l-fng). Here, we report the identification and characterisation of a second avian hairy-related gene, c-hairy2, which also cycles in the PSM and whose sequence is closely related to the mammalian HES1 gene, a downstream target of Notch signalling in vertebrates. We show that HES1 mRNA is also expressed in a cyclic fashion in the mouse PSM, similar to that observed for c-hairy1 and c-hairy2 in the chick. In HES1 mutant mouse embryos, the periodic expression of l-fng is maintained, suggesting that HES1 is not a critical component of the oscillator mechanism. In contrast, dynamic HES1 expression is lost in mice mutant for Delta1, which are defective for Notch signalling. These results suggest that Notch signalling is required for hairy-like genes cyclic expression in the PSM.


Clinical Features and Management of Non-HIV-Related Lipodystrophy in Children: A Systematic Review.
Lipodystrophy syndromes are characterized by generalized or partial absence of adipose tissue. We conducted a systematic review to synthesize data on clinical and metabolic features of lipodystrophy (age at onset, < 18 years). Sources included Medline, Embase, Cochrane Library, Scopus and Non-Indexed Citations from inception through January 2016. Search terms included lipodystrophy, and age 0 to 18 years. Patients with unambiguous diagnosis of lipodystrophy were included. Lipodystrophy secondary to HIV treatment was excluded. We identified 1141 patients from 351 studies. Generalized fat loss involving face, neck, abdomen, thorax, and upper and lower limbs was explicitly reported in 65% to 93% of patients with congenital generalized lipodystrophy (CGL) and acquired generalized lipodystrophy (AGL). In familial partial lipodystrophy (FPL), fat loss occurred from upper and lower limbs, with sparing of face and neck. In acquired partial lipodystrophy (APL), upper limbs were involved while lower limbs were spared. Other features were prominent musculature, acromegaloid, acanthosis nigricans and hepatosplenomegaly. Diabetes mellitus was diagnosed in 48% (n = 222) of patients with CGL (mean age at onset, 5.3 years). Hypertriglyceridemia was observed in CGL, AGL and FPL. Multiple interventions were used, with most patients receiving ≥ 3 interventions and being ≥ 18 years of age at the initiation of interventions. To our knowledge, this is the largest reported pooled database describing lipodystrophy patients with age at onset < 18 years. We have suggested core and supportive clinical features and summarized data on available interventions, outcomes and mortality.


Jammed packings of 3D superellipsoids with tunable packing fraction, coordination number, and ordering.
We carry out numerical studies of static packings of frictionless superellipsoidal particles in three spatial dimensions. We consider more than 200 different particle shapes by varying the three shape parameters that define superellipsoids. We characterize the structural and mechanical properties of both disordered and ordered packings using two packing-generation protocols. We perform athermal quasi-static compression simulations starting from either random, dilute configurations (Protocol 1) or thermalized, dense configurations (Protocol 2), which allows us to tune the orientational order of the packings. In general, we find that superellipsoid packings are hypostatic, with coordination number zJ < ziso, where ziso = 2df and df = 5 or 6 depending on whether the particles are axi-symmetric or not. Over the full range of orientational order, we find that the number of quartic modes of the dynamical matrix for the packings always matches the number of missing contacts relative to the isostatic value. This result suggests that there are no mechanically redundant contacts for ordered, yet hypostatic packings of superellipsoidal particles. Additionally, we find that the packing fraction at jamming onset for disordered packings of superellipsoidal depends on at least two particle shape parameters, e.g. the asphericity A and reduced aspect ratio β of the particles.


The role of auditory feedback in sustaining vocal vibrato.
Vocal vibrato and tremor are characterized by oscillations in voice fundamental frequency (F0). These oscillations may be sustained by a control loop within the auditory system. One component of the control loop is the pitch-shift reflex (PSR). The PSR is a closed loop negative feedback reflex that is triggered in response to discrepancies between intended and perceived pitch with a latency of approximately 100 ms. Consecutive compensatory reflexive responses lead to oscillations in pitch every approximately 200 ms, resulting in approximately 5-Hz modulation of F0. Pitch-shift reflexes were elicited experimentally in six subjects while they sustained /u/ vowels at a comfortable pitch and loudness. Auditory feedback was sinusoidally modulated at discrete integer frequencies (1 to 10 Hz) with +/- 25 cents amplitude. Modulated auditory feedback induced oscillations in voice F0 output of all subjects at rates consistent with vocal vibrato and tremor. Transfer functions revealed peak gains at 4 to 7 Hz in all subjects, with an average peak gain at 5 Hz. These gains occurred in the modulation frequency region where the voice output and auditory feedback signals were in phase. A control loop in the auditory system may sustain vocal vibrato and tremorlike oscillations in voice F0.


Differential host utilisation by different life history stages of the fish ectoparasite Argulus foliaceus (Crustacea: Branchiura).
In this study we examine differences in the occurrence of life history stages of the destructive fish ectoparasite Argulus foliaceus (L., 1758) on eight fish species (stickleback, rudd, roach, gudgeon, bream, tench, crucian carp and common carp) sampled from a mixed-species recreational fishing lake on nine occasions during late spring and summer. Total numbers ofA. foliaceus, as well as the number of larval, juvenile and adult parasite stages, from each fish were recorded along with the fish species. Lice generally exhibited an aggregated distribution approximating a negative binomial distribution. Significant differences in the prevalence, intensity and intensity frequency distribution were observed between life history stages and between host species. In general, all life history stages of A. foliaceus exhibited an over-dispersed distribution. However, larval lice did show some degree of aggregation particularly within the stickleback samples. Infection data for parasite larval stages suggested that sticklebacks are more likely to be infected than other host species. For adult lice, however, carp appeared to be the main host. We propose that A. foliaceus infection characteristics are predominantly determined by the level of host exposure to the parasite and its life history stages (larval, juvenile and adult) rather than by an innate difference in host susceptibility related to individual host factors such as immune responses. We conclude that host exposure is determined by the parasite-host behavioural interplay related to species-specific ecology and behavioural traits such as microhabitat preference and normal swimming speed.


Therapeutic immunization for the control of HIV-1: where are we now?
Highly active antiretroviral therapy (HAART) has transformed HIV-1 infection from an invariably fatal disease into a chronic infection requiring lifelong treatment. However, the challenges we still face are the urgent need to provide affordable sustainable therapy to the millions of infected individuals who live in resource-poor countries, and the limitations posed by serious drug toxicity and viral resistance associated with long-term therapy. Augmentation of HIV-specific immunity by therapeutic vaccination is a possible alternative to continuous HAART. In this review, progress in the development of therapeutic immunization strategies is discussed.


Accuracy of patient recall for self-reported doctor visits: Is shorter recall better?
In health economics, the use of patient recall of health care utilisation information is common, including in national health surveys. However, the types and magnitude of measurement error that relate to different recall periods are not well understood. This study assessed the accuracy of recalled doctor visits over 2-week, 3-month, and 12-month periods by comparing self-report with routine administrative Australian Medicare data. Approximately 5,000 patients enrolled in an Australian study were pseudo-randomised using birth dates to report visits to a doctor over three separate recall periods. When comparing patient recall with visits recorded in administrative information from Medicare Australia, both bias and variance were minimised for the 12-month recall period. This may reflect telescoping that occurs with shorter recall periods (participants pulling in important events that fall outside the period). Using shorter recall periods scaled to represent longer periods is likely to bias results. There were associations between recall error and patient characteristics. The impact of recall error is demonstrated with a cost-effectiveness analysis using costs of doctor visits and a regression example predicting number of doctor visits. The findings have important implications for surveying health service utilisation for use in economic evaluation, econometric analyses, and routine national health surveys.


Zwitterionic Ru(III) Complexes: Stability of Metal-Ligand Bond and Host-Guest Binding with Cucurbit[7]uril.
A wide range of ruthenium-based coordination compounds have been reported to possess potential as metallodrugs with anticancer or antimetastatic activity. In this work, we synthesized a set of new zwitterionic Ru(III) compounds bearing ligands derived from N-alkyl (R) systems based on pyridine, 4,4'-bipyridine, or 1,4-diazabicyclo[2.2.2]octane (DABCO). The effects of the ligand(s) and their environment on the coordination stability have been investigated. Whereas the [DABCO-R]+ ligand is shown to be easily split out of a negative [RuCl4]- core, positively charged R-pyridine and R-bipyridine ligands form somewhat more stable Ru(III) complexes and can be used as supramolecular anchors for binding with macrocycles. Therefore, supramolecular host-guest assemblies between the stable zwitterionic Ru(III) guests and the cucurbit[7]uril host were investigated and characterized in detail by using NMR spectroscopy and single-crystal X-ray diffraction. Paramagnetic 1H NMR experiments supplemented by relativistic DFT calculations of the structure and hyperfine NMR shifts were performed to determine the host-guest binding modes in solution. In contrast to the intramolecular hyperfine shifts, dominated by the through-bond Fermi-contact mechanism, supramolecular hyperfine shifts were shown to depend on the "through-space" spin-dipole contributions with structural trends being satisfactorily reproduced by a simple point-dipole approximation.


Enhancing Medical Student-Interpreter Collaboration in an Urban Free Clinic.
Cultural barriers and patient-provider language discordance exert deleterious effects on patient care. One solution has been the integration of medical interpreters into the care of patients with limited English proficiency. While medical schools and residency programs have started developing training programs on how to work with medical interpreters, no similar endeavor has been reported by student-run free clinics. Over 1 year, 76 third-year medical students (MS3s) were enrolled in control and intervention groups, and evaluated by in-person interpreters during interpreted real-patient encounters. MS3s in the intervention group received a lesson- and reminder-based training program on how to work with in-person interpreters. MS3s who received the intervention were more likely to ask the patient one question at a time (odds ratio [OR] 3.54, P=.0079), listen to the interpreter without unnecessary interruption (OR 3.30, P=.022), and speak in short, simple sentences with pauses for interpretation (OR 3.08, P=.017). Our lesson- and reminder-based training program on provider-interpreter collaboration can improve the performance of MS3s within a select skill set with minimal cost and time investment.


Adapting livestock management to spatio-temporal heterogeneity in semi-arid rangelands.
Management strategies in rotational grazing systems differ in their level of complexity and adaptivity. Different components of such grazing strategies are expected to allow for adaptation to environmental heterogeneities in space and time. However, most models investigating general principles of rangeland management strategies neglect spatio-temporal system properties including seasonality and spatial heterogeneity of environmental variables. We developed an ecological-economic rangeland model that combines a spatially explicit farm structure with intra-annual time steps. This allows investigating different management components in rotational grazing systems (including stocking and rotation rules) and evaluating their effect on the ecological and economic states of semi-arid grazing systems. Our results show that adaptive stocking is less sensitive to overstocking compared to a constant stocking strategy. Furthermore, the rotation rule becomes important only at stocking numbers that maximize expected income. Altogether, the best of the tested strategies is adaptive stocking combined with a rotation that adapts to both spatial forage availability and seasonality. This management strategy maximises mean income and at the same time maintains the rangeland in a viable condition. However, we could also show that inappropriate adaptation that neglects seasonality even leads to deterioration. Rangelands characterised by higher inter-annual climate variability show a higher risk of income losses under a non-adaptive stocking rule, and non-adaptive rotation is least able to buffer increasing climate variability. Overall, all important system properties including seasonality and spatial heterogeneity of available resources need to be considered when designing an appropriate rangeland management system. Resulting adaptive rotational grazing strategies can be valuable for improving management and mitigating income risks.


A decision tree algorithm for investigation of model biases related to dynamical cores and physical parameterizations.
An object-based evaluation method using a pattern recognition algorithm (i.e., classification trees) is applied to the simulated orographic precipitation for idealized experimental setups using the National Center of Atmospheric Research (NCAR) Community Atmosphere Model (CAM) with the finite volume (FV) and the Eulerian spectral transform dynamical cores with varying resolutions. Daily simulations were analyzed and three different types of precipitation features were identified by the classification tree algorithm. The statistical characteristics of these features (i.e., maximum value, mean value, and variance) were calculated to quantify the difference between the dynamical cores and changing resolutions. Even with the simple and smooth topography in the idealized setups, complexity in the precipitation fields simulated by the models develops quickly. The classification tree algorithm using objective thresholding successfully detected different types of precipitation features even as the complexity of the precipitation field increased. The results show that the complexity and the bias introduced in small-scale phenomena due to the spectral transform method of CAM Eulerian spectral dynamical core is prominent, and is an important reason for its dissimilarity from the FV dynamical core. The resolvable scales, both in horizontal and vertical dimensions, have significant effect on the simulation of precipitation. The results of this study also suggest that an efficient and informative study about the biases produced by GCMs should involve daily (or even hourly) output (rather than monthly mean) analysis over local scales.


Exploratory Study on Application of MALDI-TOF-MS to Detect SARS-CoV-2 Infection in Human Saliva.
SARS-CoV-2 has caused a large outbreak since its emergence in December 2019. COVID-19 diagnosis became a priority so as to isolate and treat infected individuals in order to break the contamination chain. Currently, the reference test for COVID-19 diagnosis is the molecular detection (RT-qPCR) of the virus from nasopharyngeal swab (NPS) samples. Although this sensitive and specific test remains the gold standard, it has several limitations, such as the invasive collection method, the relative high cost and the duration of the test. Moreover, the material shortage to perform tests due to the discrepancy between the high demand for tests and the production capacities puts additional constraints on RT-qPCR. Here, we propose a PCR-free method for diagnosing SARS-CoV-2 based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling and machine learning (ML) models from salivary samples. Kinetic saliva samples were collected at enrollment and ten and thirty days later (D0, D10 and D30), to assess the classification performance of the ML models compared to the molecular tests performed on NPS specimens. Spectra were generated using an optimized protocol of saliva collection and successive quality control steps were developed to ensure the reliability of spectra. A total of 360 averaged spectra were included in the study. At D0, the comparison of MS spectra from SARS-CoV-2 positive patients (n = 105) with healthy healthcare controls (n = 51) revealed nine peaks that significantly distinguished the two groups. Among the five ML models tested, support vector machine with linear kernel (SVM-LK) provided the best performance on the training dataset (accuracy = 85.2%, sensitivity = 85.1%, specificity = 85.3%, F1-Score = 85.1%). The application of the SVM-LK model on independent datasets confirmed its performances with 88.9% and 80.8% of correct classification for samples collected at D0 and D30, respectively. Conversely, at D10, the proportion of correct classification had fallen to 64.3%. The analysis of saliva samples by MALDI-TOF MS and ML appears as an interesting supplementary tool for COVID-19 diagnosis, despite the mitigated results obtained for convalescent patients (D10).


Back pain, mental health and substance use are associated in adolescents.
During adolescence, prevalence of pain and health risk factors such as smoking, alcohol use and poor mental health all rise sharply. The aim of this study was to describe the relationship between back pain and health risk factors in adolescents. Cross-sectional data from the Healthy Schools Healthy Futures study, and the Australian Child Wellbeing Project was used, mean age: 14-15 years. Children were stratified according to back pain frequency. Within each strata, the proportion of children that reported drinking alcohol or smoking or that experienced feelings of anxiety or depression was reported. Test-for-trend analyses assessed whether increasing frequency of pain was associated with health risk factors. Data was collected from ~2500 and 3900 children. Larger proportions of children smoked or drank alcohol within each strata of increasing pain frequency. The trend with anxiety and depression was less clear, although there was a marked difference between the children that reported no pain, and pain more frequently. Two large, independent samples show adolescents that experience back pain more frequently are also more likely to smoke, drink alcohol and report feelings of anxiety and depression. Pain appears to be part of the picture of general health risk in adolescents.


Photo/thermoresponsive ABC triblock copolymer-based ion gels: photoinduced structural transitions.
A photo/thermoresponsive ABC triblock copolymer-based ion gel exhibiting photoinduced structural transitions accompanied by significant rheological changes is newly developed. The ABC triblock copolymer comprises an ionic liquid (IL)-phobic A block, an IL-philic B block, and a photo/thermoresponsive C block containing azobenzene moieties. The IL-phobic A block forms a rigid micellar core in an IL over a wide temperature range and the photo/thermoresponsive C block undergoes upper critical solution temperature (UCST)-type phase transition in ILs. In concentrated polymer solution, the ABC triblock copolymer can form a percolated micellar network at low temperatures through aggregation of A and C blocks as physical crosslinks, bridged by IL-philic B blocks. In contrast, the ion gel undergoes structural transition to jammed micelles at high temperatures due to the disassembly of the thermoresponsive C block, resulting in significant softening of the ion gel. Importantly, the temperature dependences of the viscoelastic properties of the ion gel differ drastically depending on photo-irradiation conditions as the photoinduced isomerization of azobenzene moieties in the C block modulates the affinity between the polymer chain and IL. Utilizing this feature, photoinduced softening/hardening of the ion gel is realized at constant temperature. This study provides a promising strategy to control the rheological properties of nonvolatile soft materials via contactless light irradiation that could be exploited in various applications such as photoresponsive soft actuators and photo-healable soft materials.


High-throughput endogenous measurement of S-nitrosylation in Alzheimer's disease using oxidized cysteine-selective cPILOT.
Reversible cysteine modifications play important physiological roles such as modulating enzymatic catalysis, maintaining redox homeostasis and conducting cellular signaling. These roles can be critical in the context of disease. Oxidative modifications such as S-nitrosylation (SNO) are signatures of neurodestruction in conditions of oxidative stress however are also indicators of neuroprotection and normal signaling in cellular environments with low concentrations of reactive oxygen and nitrogen species. SNO is a dynamic and low abundance modification and requires sensitive and selective analytical methods for its detection in biological tissues. Here we present an enhanced multiplexing strategy to study SNO in complex mixtures arising from tissues. This method, termed oxidized cysteine-selective cPILOT (OxcyscPILOT), allows simultaneous analysis of SNO-modified peptides in 12 samples. OxcyscPILOT has three primary steps: (1) blocking of free thiols by a cysteine-reactive reagent, (2) enrichment of peptides containing SNO on a solid phase resin, and (3) isotopic labeling and isobaric tagging of enriched peptides on the solid phase resin. This approach offers the advantage of allowing total protein abundance levels to be measured simultaneously with endogenous SNO levels and measurement of SNO levels across four biological replicates in a single analysis. Furthermore, the relative amount of SNO on a specific cysteine site can also be determined. A well-known model of Alzheimer's disease, the APP/PS-1 transgenic mouse model, was selected for demonstration of the method as several SNO-modified proteins have previously been reported in brain and synaptosomes from AD subjects. OxcyscPILOT analysis resulted in identification of 138 SNO-modified cysteines in brain homogenates that correspond to 135 proteins. Many of these SNO-modified proteins were only present in wild-type or AD mice, whereas 93 proteins had SNO signals in both WT and AD. Pathway analysis links SNO-modified proteins to various biological pathways especially metabolism and signal transduction, consistent with previous reports in the literature. The OxcyscPILOT strategy provides enhanced multiplexing capability to current redox proteomics methods to study oxidative modifications of cysteine.


Barriers to care in an ethnically diverse publicly insured population: is health care reform enough?
The Affordable Care Act provides for the expansion of Medicaid, which may result in as many as 16 million people gaining health insurance coverage. Yet it is unclear to what extent this coverage expansion will meaningfully increase access to health care. The objective of the study was to identify barriers that may persist even after individuals are moved to insurance and to explore racial/ethnic variation in problems accessing health care services. Data are from a 2008 cross-sectional mixed-mode survey (mail with telephone follow-up in 4 languages), which is unique in measuring a comprehensive set of barriers and in focusing on several select understudied ethnic groups. We examine racial/ethnic variation in cost and coverage, access, and provider-related barriers. The study adhered to a community-based participatory research process. Surveys were obtained from a stratified random sample of adults enrolled in Minnesota Health Care Programs who self-report ethnicity as white, African American, American Indian, Hispanic, Hmong, or Somali (n=1731). All enrollees reported barriers to getting needed care; enrollees from minority cultural groups (Hmong and American Indian in particular) were more likely to experience problems than whites. Barriers associated with cost and coverage were the most prevalent, with 72% of enrollees reporting 1 or more of these problems. Approximately 63% of enrollees reported 1 or more access barriers. Provider-related barriers were the least prevalent (about 29%) yet revealed the most pervasive disparities. Many challenges to care persist for publicly insured adults, particularly minority racial and ethnic groups. The ACA expansion of Medicaid, although necessary, is not sufficient for achieving improved and equitable access to care.


Alcohol drinking and risks of liver cancer and non-neoplastic chronic liver diseases in China: a 10-year prospective study of 0.5 million adults.
Alcohol consumption is an important risk factor for hepatic neoplastic and non-neoplastic diseases. Questions remain, however, about the relevance to disease risk of drinking patterns and alcohol tolerability, which differ appreciably between Chinese and Western populations. The prospective China Kadoorie Biobank included 512,715 adults (41% men) aged 30-79 years recruited from ten areas during 2004-2008, recording alcohol intake, drinking patterns, and other characteristics. After median 10 years' follow-up, 2531 incident liver cancer, 2040 liver cirrhosis, 260 alcoholic liver disease (ALD), and 1262 non-alcoholic fatty liver disease (NAFLD) cases were recorded among 492,643 participants without prior cancer or chronic liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) relating alcohol intake and drinking patterns to each disease. Overall, 33% of men and 2% of women drank alcohol regularly (i.e. at least weekly) at baseline. Among male current regular drinkers, alcohol consumption showed positive dose-response associations with risks of several major chronic liver diseases, with HRs per 280 g/week (i.e. around four drinks/day) higher usual alcohol intake of 1.44 (95% CI 1.23-1.69) for liver cancer (n = 547), 1.83 (1.60-2.09) for liver cirrhosis (n = 388), 2.01 (1.77-2.28) for ALD (n = 200), 1.71 (1.35-2.16) for NAFLD (n = 198), and 1.52 (1.40-1.64) for total liver disease (n = 1775). The association with ALD appeared stronger among men reporting flushing (i.e., with low alcohol tolerance). After adjustment for the total amount of weekly alcohol consumption, daily drinkers had significantly increased risk of ALD (2.15, 1.40-3.31) compared with non-daily drinkers, and drinking without meals was associated with significantly greater risks of liver cancer (1.32, 1.01-1.72), liver cirrhosis (1.37, 1.02-1.85), and ALD (1.60, 1.09-2.33) compared with drinking with meals. Female current regular drinkers had significantly higher risk of ALD, but not other liver diseases, than female abstainers. In Chinese men, alcohol intake was associated with significantly increased risks of several major chronic liver diseases, and certain drinking patterns (e.g. drinking daily, drinking without meals) may further exacerbate the disease risks.


Brand name to generic substitution of levetiracetam in patients with epilepsy.
Levetiracetam is one of the most widely used antiepileptic drugs, but the evidence related to the safety of substitution from brand name to generic levetiracetam is scarce. The present study evaluated the risk of increased frequency of seizures after replacement of a brand-name levetiracetam with a generic product. We enrolled patients with epilepsy who were treated with branded levetiracetam for at least 6 months of sustained use. Patients were advised to switch to the generic levetiracetam. We analyzed data from 6 months before, to 6 months after, generic substitution. Increased seizure frequency was defined as a≥ 50% increase in seizure frequency after conversion date compared with seizure frequency before the conversion date. We analyzed changes in seizure frequency and performed subgroup analysis according to changes in seizure frequency. We analyzed 148 epilepsy patients. Among the 148 patients, 109 (73.6%) were seizure-free before substitution and 105 patients remained seizure-free after switching. After generic substitution, an increased seizure frequency was noted in seven patients (4.7%), and a decreased seizure frequency was noted in 10 (6.8%). Patients with decreased seizure frequency were significantly younger (p = 0.035) than those with an unchanged seizure frequency. This study suggests that the risk of increased seizure frequency after generic substitution was minimal. The generic substitution of levetiracetam was generally safe, although larger prospective studies are warranted to corroborate our findings.


Tissue-specific mRNA expression profiling in grape berry tissues.
Berries of grape (Vitis vinifera) contain three major tissue types (skin, pulp and seed) all of which contribute to the aroma, color, and flavor characters of wine. The pericarp, which is composed of the exocarp (skin) and mesocarp (pulp), not only functions to protect and feed the developing seed, but also to assist in the dispersal of the mature seed by avian and mammalian vectors. The skin provides volatile and nonvolatile aroma and color compounds, the pulp contributes organic acids and sugars, and the seeds provide condensed tannins, all of which are important to the formation of organoleptic characteristics of wine. In order to understand the transcriptional network responsible for controlling tissue-specific mRNA expression patterns, mRNA expression profiling was conducted on each tissue of mature berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip(R) Vitis oligonucleotide microarray ver. 1.0. In order to monitor the influence of water-deficit stress on tissue-specific expression patterns, mRNA expression profiles were also compared from mature berries harvested from vines subjected to well-watered or water-deficit conditions. Overall, berry tissues were found to express approximately 76% of genes represented on the Vitis microarray. Approximately 60% of these genes exhibited significant differential expression in one or more of the three major tissue types with more than 28% of genes showing pronounced (2-fold or greater) differences in mRNA expression. The largest difference in tissue-specific expression was observed between the seed and pulp/skin. Exocarp tissue, which is involved in pathogen defense and pigment production, showed higher mRNA abundance relative to other berry tissues for genes involved with flavonoid biosynthesis, pathogen resistance, and cell wall modification. Mesocarp tissue, which is considered a nutritive tissue, exhibited a higher mRNA abundance of genes involved in cell wall function and transport processes. Seeds, which supply essential resources for embryo development, showed higher mRNA abundance of genes encoding phenylpropanoid biosynthetic enzymes, seed storage proteins, and late embryogenesis abundant proteins. Water-deficit stress affected the mRNA abundance of 13% of the genes with differential expression patterns occurring mainly in the pulp and skin. In pulp and seed tissues transcript abundance in most functional categories declined in water-deficit stressed vines relative to well-watered vines with transcripts for storage proteins and novel (no-hit) functional assignments being over represented. In the skin of berries from water-deficit stressed vines, however, transcripts from several functional categories including general phenypropanoid and ethylene metabolism, pathogenesis-related responses, energy, and interaction with the environment were significantly over-represented. These results revealed novel insights into the tissue-specific expression mRNA expression patterns of an extensive repertoire of genes expressed in berry tissues. This work also establishes an extensive catalogue of gene expression patterns for future investigations aimed at the dissection of the transcriptional regulatory hierarchies that govern tissue-specific expression patterns associated with tissue differentiation within berries. These results also confirmed that water-deficit stress has a profound effect on mRNA expression patterns particularly associated with the biosynthesis of aroma and color metabolites within skin and pulp tissues that ultimately impact wine quality.


Reconstitution of Schwannian stroma in neuroblastomas using human bone marrow stromal cells.
The Schwannian stroma in neuroblastomas is related to patient prognosis. There is debate surrounding the origin of Schwannian stroma in neuroblastomas: one theory is that the Schwann cells are derived from neoplastic cells, and the other is that they arise from normal cells surrounding the neuroblastoma. We examined whether human bone marrow stromal cells (hBMSCs) or human mesenchymal stem cells (hMSCs) could differentiate into Schwann cells in neuroblastomas. hBMSCs or hMSCs along with enhanced green fluorescent protein (EGFP) were injected into xenotransplanted neuroblastomas in nonobese diabetic mice with severe combined immunodeficiency and the resulting tumors were analyzed using immunohistochemistry. HBMSCs and hMSCs were co-cultured with neuroblastoma cells, and the induction of Schwann cell-specific molecules, S100beta and Egr-2, was monitored. S100beta-positive Schwannian stroma was observed only in neuroblastomas containing either hBMSCs or hMSCs, but not in neuroblastomas lacking these cells. Double staining with anti-S100 and anti-EGFP antibodies showed that S100-positive cells in neuroblastomas were also EGFP-positive. By contrast, hBMSCs did not develop into Schwann cells in Ewing's sarcoma, demonstrating that differentiation of transplanted hBMSCs or hMSCs into Schwann cells occurs specifically in neuroblastomas. Both S100beta and Egr-2 were expressed in hBMSCs or hMSCs co-cultured with neuroblastoma cells. HBMSCs or hMSCs may contribute to the formation of human tumor stroma. The Schwannian stroma of neuroblastomas appears to be derived from nonneoplastic stromal cells rather than neuroblastoma cells, further clarifying its developmental origins.


Can Homeopathy, a Particularly Mild Therapeutic Approach, Survive and Grow in a World of Violence?
This short treatise addresses a philosophical question concerning the place of homeopathy in our modern world. The question raised is whether a therapeutic system as peaceful, mild, and non-violent as homeopathy can survive and grow within a society that often displays the opposite characteristics.Much of contemporary society is more interested in fast and impressive cures, even if these may also bring side effects; whereas homeopathy can offer solutions with a personalized approach that requires long hours of case study by the homeopath to find the correct personal remedy that aims to bring about positive results, which the therapy can produce in deep chronic diseases.The conclusion drawn is that homeopathy does not readily fit within a modern and violent society that prefers quick and invasive solutions to its clinical problems.


Patient blood management: a fresh look at a fresh approach to blood transfusion.
The overall use of allogeneic blood transfusions in clinical practice remains relatively high and still varies widely among centres and practitioners. Moreover, allogeneic blood transfusions have historically been linked with risks and complications: some of them (e.g. transfusion reactions and transmission of pathogens) have been largely mitigated through advancements in blood banking whereas some others (e.g. immunomodulation and transfusion-related acute lung injury) appear to have more subtle etiologies and are more difficult to tackle. Furthermore, blood transfusions are costly and the supply of blood is limited. Finally, evidence indicates that a great number of the critically ill patients who are being transfused today may not be having tangible benefits from the transfusion. Patient blood management is an evidence-based, multidisciplinary, multimodal, and patient-tailored approach aimed at reducing or eliminating the need for allogeneic transfusion by managing anaemia, perioperative blood conservation, surgical haemostasis, and blood as well as plasma-derivative drug use. From this point of view, the reduction of allogeneic blood usage is not an end in itself but a tool to achieve better patient clinical outcome. This article focuses on the three-pillar matrix of patient blood management where the understanding of basic physiology and pathophysiology is at the core of evidence-based approaches to optimizing erythropoiesis, minimising bleeding and tolerating anemia. Anesthesiologists and critical care physicians clearly have a key role in patient blood management programmes are and should incorporate its principles into clinical practice-based initiatives that improve patient safety and clinical outcomes.


A Cox-Based Risk Prediction Model for Early Detection of Cardiovascular Disease: Identification of Key Risk Factors for the Development of a 10-Year CVD Risk Prediction.
Current cardiovascular disease (CVD) risk models are typically based on traditional laboratory-based predictors. The objective of this research was to identify key risk factors that affect the CVD risk prediction and to develop a 10-year CVD risk prediction model using the identified risk factors. A Cox proportional hazard regression method was applied to generate the proposed risk model. We used the dataset from Framingham Original Cohort of 5079 men and women aged 30-62 years, who had no overt symptoms of CVD at the baseline; among the selected cohort 3189 had a CVD event. A 10-year CVD risk model based on multiple risk factors (such as age, sex, body mass index (BMI), hypertension, systolic blood pressure (SBP), cigarettes per day, pulse rate, and diabetes) was developed in which heart rate was identified as one of the novel risk factors. The proposed model achieved a good discrimination and calibration ability with C-index (receiver operating characteristic (ROC)) being 0.71 in the validation dataset. We validated the model via statistical and empirical validation. The proposed CVD risk prediction model is based on standard risk factors, which could help reduce the cost and time required for conducting the clinical/laboratory tests. Healthcare providers, clinicians, and patients can use this tool to see the 10-year risk of CVD for an individual. Heart rate was incorporated as a novel predictor, which extends the predictive ability of the past existing risk equations.


Developing a biocuration workflow for AgBase, a non-model organism database.
AgBase provides annotation for agricultural gene products using the Gene Ontology (GO) and Plant Ontology, as appropriate. Unlike model organism species, agricultural species have a body of literature that does not just focus on gene function; to improve efficiency, we use text mining to identify literature for curation. The first component of our annotation interface is the gene prioritization interface that ranks gene products for annotation. Biocurators select the top-ranked gene and mark annotation for these genes as 'in progress' or 'completed'; links enable biocurators to move directly to our biocuration interface (BI). Our BI includes all current GO annotation for gene products and is the main interface to add/modify AgBase curation data. The BI also displays Extracting Genic Information from Text (eGIFT) results for each gene product. eGIFT is a web-based, text-mining tool that associates ranked, informative terms (iTerms) and the articles and sentences containing them, with genes. Moreover, iTerms are linked to GO terms, where they match either a GO term name or a synonym. This enables AgBase biocurators to rapidly identify literature for further curation based on possible GO terms. Because most agricultural species do not have standardized literature, eGIFT searches all gene names and synonyms to associate articles with genes. As many of the gene names can be ambiguous, eGIFT applies a disambiguation step to remove matches that do not correspond to this gene, and filtering is applied to remove abstracts that mention a gene in passing. The BI is linked to our Journal Database (JDB) where corresponding journal citations are stored. Just as importantly, biocurators also add to the JDB citations that have no GO annotation. The AgBase BI also supports bulk annotation upload to facilitate our Inferred from electronic annotation of agricultural gene products. All annotations must pass standard GO Consortium quality checking before release in AgBase. Database URL: http://www.agbase.msstate.edu/.


Computational models of Bitemporal, Bifrontal and Right Unilateral ECT predict differential stimulation of brain regions associated with efficacy and cognitive side effects.
Extensive clinical research has shown that the efficacy and cognitive outcomes of electroconvulsive therapy (ECT) are determined, in part, by the type of electrode placement used. Bitemporal ECT (BT, stimulating electrodes placed bilaterally in the frontotemporal region) is the form of ECT with relatively potent clinical and cognitive side effects. However, the reasons for this are poorly understood. This study used computational modelling to examine regional differences in brain excitation between BT, Bifrontal (BF) and Right Unilateral (RUL) ECT, currently the most clinically-used ECT placements. Specifically, by comparing similarities and differences in current distribution patterns between BT ECT and the other two placements, the study aimed to create an explanatory model of critical brain sites that mediate antidepressant efficacy and sites associated with cognitive, particularly memory, adverse effects. High resolution finite element human head models were generated from MRI scans of three subjects. The models were used to compare differences in activation between the three ECT placements, using subtraction maps. In this exploratory study on three realistic head models, Bitemporal ECT resulted in greater direct stimulation of deep midline structures and also left temporal and inferior frontal regions. Interpreted in light of existing knowledge on depressive pathophysiology and cognitive neuroanatomy, it is suggested that the former sites are related to efficacy and the latter to cognitive deficits. We hereby propose an approach using binarised subtraction models that can be used to optimise, and even individualise, ECT therapies.


When the inhibitor tells more than the substrate: the cyanide-bound state of a carbon monoxide dehydrogenase.
Carbon monoxide dehydrogenase (CODH) is a key enzyme for reversible CO interconversion. To elucidate structural and mechanistic details of CO binding at the CODH active site (C-cluster), cyanide is frequently used as an iso-electronic substitute and inhibitor. However, previous studies revealed conflicting results on the structure of the cyanide-bound complex and the mechanism of cyanide-inhibition. To address this issue in this work, we have employed IR spectroscopy, crystallography, site directed mutagenesis, and theoretical methods to analyse the cyanide complex of the CODH from Carboxydothermus hydrogenoformans (CODHII Ch ). IR spectroscopy demonstrates that a single cyanide binds to the Ni ion. Whereas the inhibitor could be partially removed at elevated temperature, irreversible degradation of the C-cluster occurred in the presence of an excess of cyanide on the long-minute time scale, eventually leading to the formation of [Fe(CN)6]4- and [Ni(CN)4]2- complexes. Theoretical calculations based on a new high-resolution structure of the cyanide-bound CODHII Ch indicated that cyanide binding to the Ni ion occurs upon dissociation of the hydroxyl ligand from the Fe1 subsite of the C-cluster. The hydroxyl group is presumably protonated by Lys563 which, unlike to His93, does not form a hydrogen bond with the cyanide ligand. A stable deprotonated ε-amino group of Lys563 in the cyanide complex is consistent with the nearly unchanged C[triple bond, length as m-dash]N stretching in the Lys563Ala variant of CODHII Ch . These findings support the view that the proton channel connecting the solution phase with the active site displays a strict directionality, controlled by the oxidation state of the C-cluster.


Conceptualisations of landscape differ across European languages.
Policies aimed at sustainable landscape management recognise the importance of multiple cultural viewpoints, but the notion of landscape itself is implicitly assumed to be homogeneous across speech communities. We tested this assumption by collecting data about the concept of "landscape" from speakers of seven languages of European origin. Speakers were asked to freely list exemplars to "landscape" (a concrete concept for which the underlying conceptual structure is unclear), "animals" (a concrete and discrete concept) and "body parts" (a concrete concept characterised by segmentation). We found, across languages, participants considered listing landscape terms the hardest task, listed fewest exemplars, had the least number of shared exemplars, and had fewer common co-occurrence pairs (i.e., pairs of exemplars listed adjacently). We also found important differences between languages in the types of exemplars that were cognitively salient and, most importantly, in how the exemplars are connected to each other in semantic networks. Overall, this shows that "landscape" is more weakly structured than other domains, with high variability both within and between languages. This diversity suggests that for sustainable landscape policies to be effective, they need to be better tailored to local conceptualisations.


Lysobacter concretionis sp. nov., isolated from anaerobic granules in an upflow anaerobic sludge blanket reactor.
The taxonomic positions of Lysobacter species with validly published names and a novel strain Ko07(T), which was newly isolated from an upflow anaerobic sludge blanket reactor treating wastewater from a brewery, were (re)estimated on the basis of results obtained by using a polyphasic taxonomy approach. Phylogenetic inference based on 16S rRNA gene sequences showed that strain Ko07(T) and all Lysobacter species with validly published names clustered together in a phylogenetic branch within the class 'Gammaproteobacteria'. The sequence similarity of strain Ko07(T) to the type strains of established Lysobacter species was in the range 94.9-96.7 %. Ubiquinone Q-8 and branched fatty acids, C(11 : 0) iso, C(15 : 0) iso, C(16 : 0) iso, iso C(17 : 1)omega9c and C(11 : 0) iso 3OH, predominantly appeared in strain Ko07(T) as well as in all type strains of the recognized Lysobacter species. The DNA-DNA hybridization values of strain Ko07(T) with those of recognized Lysobacter species were estimated to be 2-20 %. Despite sharing common taxonomic features in important phenotypic characteristics, such as gliding movement, long-rod shape and proteolytic activity, strain Ko07(T) could be distinguished from the Lysobacter species with validly published names by its low DNA-DNA hybridization value, a comparatively low DNA G + C content (63.8 mol%), substrate utilization and some physiochemical characteristics. On the basis of the results obtained in this study, it is proposed that strain Ko07(T) should be classified as representing a novel member of the genus Lysobacter, for which the name Lysobacter concretionis sp. nov. is proposed. The type strain is Ko07(T) (=KCTC 12205(T) = DSM 16239(T)).


Adolescents' perceptions of family social status correlate with health and life chances: A twin difference longitudinal cohort study.
Children from lower-income households are at increased risk for poor health, educational failure, and behavioral problems. This social gradient is one of the most reproduced findings in health and social science. How people view their position in social hierarchies also signals poor health. However, when adolescents' views of their social position begin to independently relate to well-being is currently unknown. A cotwin design was leveraged to test whether adolescents with identical family backgrounds, but who viewed their family's social status as higher than their same-aged and sex sibling, experienced better well-being in early and late adolescence. Participants were members of the Environmental Risk Longitudinal Twin Study, a representative cohort of British twins (n = 2,232) followed across the first 2 decades of life. By late adolescence, perceptions of subjective family social status (SFSS) robustly correlated with multiple indicators of health and well-being, including depression; anxiety; conduct problems; marijuana use; optimism; not in education, employment, or training (NEET) status; and crime. Findings held controlling for objective socioeconomic status both statistically and by cotwin design after accounting for measures of childhood intelligence (IQ), negative affect, and prior mental health risk and when self-report, informant report, and administrative data were used. Little support was found for the biological embedding of adolescents' perceptions of familial social status as indexed by inflammatory biomarkers or cognitive tests in late adolescence or for SFSS in early adolescence as a robust correlate of well-being or predictor of future problems. Future experimental studies are required to test whether altering adolescents' subjective social status will lead to improved well-being and social mobility.


Distribution of household disinfection kits during the 2014-2015 Ebola virus outbreak in Monrovia, Liberia: The MSF experience.
During the initial phase of the 2014-2016 Ebola virus disease (EVD) outbreak in Monrovia, Liberia, all hospitals' isolation capacities were overwhelmed by the sheer caseload. As a stop-gap measure to halt transmission, Medecins sans Frontieres (MSF) distributed household disinfection kits to those who were at high risk of EVD contamination. The kit contained chlorine and personal protective materials to be used for the care of a sick person or the handling of a dead body. This intervention was novel and controversial for MSF. This paper shed the light on this experience of distribution in Monrovia and assess if kits were properly used by recipients. Targeted distribution was conducted to those at high risk of EVD (relatives of confirmed EVD cases) and health staff. Mass distributions were also conducted to households in the most EVD affected urban districts. A health promotion strategy focused on the purpose and use of the kit was integrated into the distribution. Follow-up phone calls to recipients were conducted to enquire about the use of the kit. Overall, 65,609 kits were distributed between September and November 2014. A total of 1,386 recipients were reached by phone. A total of 60 cases of sickness and/or death occurred in households who received a kit. The majority of these (46, 10%) were in households of relatives of confirmed EVD cases. Overall, usage of the kits was documented in 56 out of 60 affected households. Out of the 1322 households that did not experience sickness and/or death after the distribution, 583 (44%) made use of elements of the kit, mainly (94%) chlorine for hand-washing. At the peak of an EVD outbreak, the distribution of household disinfection kits was feasible and kits were appropriately used by the majority of recipients. In similar circumstances in the future, the intervention should be considered.


Evaluation of a rapid HIV testing initiative in an urban, hospital-based dental clinic.
Performing rapid HIV testing in nontraditional clinical settings such as dental clinics is a potential method for targeting high-risk individuals who may not otherwise access health care settings that offer HIV testing. In March 2008, Harlem Hospital Center, located in New York City, launched a counselor-based rapid HIV testing initiative in its on-site dental clinic. A full-time, trained counselor consented and tested patients as they waited for their appointments. HIV screening was performed using a whole-blood, finger-stick rapid HIV test. Through this initiative, 3864 HIV tests were performed from March 1, 2008 to December 31, 2009, representing 3565 unique individuals and 97.6% of dental patients approached for testing. Of those tested, the mean age was 38.5 years, with 47.1% female, 75.5% black, and 20.6% Hispanic. Self-reported HIV risk behaviors included 73.5% with recent unprotected heterosexual intercourse, 4.6% with recent or past injection drug use, and 2.6% who identified as men who have sex with men. Nineteen previously undiagnosed individuals (0.53%) were confirmed HIV positive. Of these individuals, mean age was 38.3 years with males representing 84.2%. Fifteen newly diagnosed patients (78.9%) were linked to care. Of those linked to care, median initial CD4 cell count was 317 cells/mm(3); 6 of these individuals (40%) had CD4 cell counts below 200 cells/mm(3). Our results demonstrate that a counselor-based rapid HIV testing program with linkage to specialized HIV care can be successfully integrated into the dental clinic setting.