Supporting grandchildren's remote instruction during COVID-19: Experiences of custodial grandmothers.
While negative impacts of COVID-19-related remote instruction on children continue to emerge, it appears that vulnerable students will disproportionately bear the burden. One such vulnerable population is children being raised by grandparents. The purpose of this mixed methods study was to gain insight into custodial grandmothers' (CGMs) experiences of their grandchildren's remote instruction, as well as individual and contextual factors associated with these experiences. A national sample of 315 CGMs, drawn from two randomized clinical trials, completed an online survey in Spring of 2020. Results of a thematic analysis and supplemental quantitative analyses revealed three themes. First, access to technology and instructional supports were critical to the success of remote instruction, with barriers being difficulties using technology and poor-quality remote instruction. Next, grandchild socioemotional difficulties, and fit with remote instruction, were central to their engagement and success with remote instruction. Finally, CGMs experienced multiple stressors related to managing the demands of remote instruction, work, and family. Challenges associated with remote instruction were related to pre-pandemic difficulties such as grandchild problems and CGM depressive symptoms. Collectively, the results highlight how multiple adversities may have amplified grandchildren's existing vulnerability to negative outcomes. Implications are addressed, including strategies for supporting children raised by grandparents beyond the COVID-19 pandemic.


Antimicrobial efficiency of Tinospora cordifolia and Ocimum tenuiflorum against Streptococcus mutans and Candida albicans.
The application of traditional medicinal plants and their products for treatment has been an integral part of our culture and continues to play a key role as many infectious microorganisms are resistant to synthetic drugs. Tinospora cordifolia and Ocimum tenuiflorum herbs have shown medicinal properties and have gained importance in modern research. This study assessed the antimicrobial activities of Tinospora cordifolia and Ocimum tenuiflorum against Streptococcus mutans and Candida albicans to conventional medications such as chlorhexidine and nystatin. The S. mutans and C. albicans were grown and maintained on Columbia agar plates and yeast malt extract agar respectively. An ethanolic extract was made and subjected to rotary evaporation to remove the ethanol. The antimicrobial activity of plant extracts was determined using the Kirby-Bauer disc diffusion method. The standard drugs, 10 μg/disc nystatin and 0.12% chlorhexidine, were used as a positive control. The zone of inhibition was measured after 24 hours. At a concentration of 3 mgs., the zone of inhibition of 25.6 mm was found with T. cordifolia, followed by 15.8 mm with O. tenuiflorum against S. mutans, and 0.12% chlorhexidine, at 21.7 ± 0.43 mm. A zone of inhibition of 23 mm and 22.9 mm was observed in both T. cordifolia and O. tenuiflorum against C. albicans, respectively. Positive control of nystatin showed 26.1 ± 0.46 mm. Tinospora cordifolia has better antimicrobial activity against S. mutans compared to Ocimum tenuiflorum. Whereas at higher concentrations, both extracts were effective against C. albicans.


Assessment of the adherence of community health workers to dosing and referral guidelines for the management of fever in children under 5 years: a study in Dangme West District, Ghana.
Community health workers (CHW) manage simple childhood illnesses in many developing countries. Information on CHWs' referral practices is limited. As part of a large cluster-randomised trial, this study assessed CHWs' adherence to dosing and referral guidelines. Records of consultations of children aged 2-59 months with fever managed by CHWs were analysed. Appropriate use of drugs was defined as provision of the correct drug pack(s) for the child's age group. Symptoms requiring referral were categorised into danger signs, respiratory distress and symptoms indicating other illnesses. Multivariate logistic regression examined symptoms most likely to be noted as requiring referral and those associated with provision of a written referral. Most children (11 659/12 330; 94.6%) received the appropriate drug. Only 161 of 1758 (9.2%) children who, according to the guidelines required referral were provided with a written referral. Not drinking/breastfeeding, persistent vomiting, unconsciousness/lethargy, difficultly breathing, fast breathing, bloody stool, sunken eyes and pallor were symptoms significantly associated with being identified by CHWs as needing referral or receiving a written referral. CHWs' adherence to dosing guidelines was high. Adherence to referral guidelines was inadequate. More effort needs to be put into strengthening referral practices of CHWs within comparable community programmes.


Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia.
The development of effective drugs for the treatment of dementia is an important therapeutic target. Drugs which stop the progression of dementia have not been developed; however, nootropics and metabolically active compounds such as the vinca alkaloids and the ergot alkaloids as well as alkylxanthines are widely used to alleviate the symptoms. This review summarises animal studies investigating the mechanism of action of these compounds and highlights gaps in our knowledge of their pharmacology. Nootropics, such as piracetam, facilitate learning and retrieval of information and protect the brain from physical and chemical intoxication. Nootropics may produce these effects via an enhancement of acetylcholine or dopamine release; however, this postulate requires further evaluation. The pharmacology of vinca alkaloids is reviewed with particular reference to vinpocetine. This compound attenuates cognitive deficits, reduces ischaemia-induced hippocampal cell loss and increases cerebral blood flow and glucose utilisation. These effects may be induced by modulation of cyclic nucleotide levels and adenosine re-uptake inhibition. An extensively examined ergot alkaloid is co-dergocrine; this compound increases both the oxygen tension and the electrical activity of the ischaemic cerebral cortex. Alkylxanthines have a wide range of pharmacological activities, and in this review the pharmacology of pentoxifylline, propentofylline and denbufylline is contrasted with that of theophylline and caffeine. In particular, the pharmacology of propentofylline and the selective low Km cyclic AMP phosphodiesterase inhibitor denbufylline is summarised. Although more carefully controlled clinical trials in well defined patient collectives are required, present evidence suggests some therapeutic efficacy for nootropics and metabolically active compounds. Further studies to more closely evaluate their mechanism of action may lead to the development of more effective agents for the therapy of dementia.


Long-term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind, multicenter trial.
The purpose of this multicenter, double-blind, randomized, parallel-group study was to determine the effect of thirteen 28-day cycles of drospirenone combined with estradiol, compared with estradiol alone, on the endometrium of postmenopausal women. Postmenopausal women not on hormone therapy but with an intact uterus were enrolled (N = 1,147); 1,142 were evaluated. Participants were randomly assigned to treatment with 1.0 mg of estradiol alone (E(2) monotherapy) or 1.0 mg of estradiol plus 0.5, 1.0, 2.0, or 3.0 mg of drospirenone (DRSP/E(2)). Endometrial biopsies were performed at baseline, at 7 months if indicated, and at study end in the 13th month. Safety was evaluated with peripheral blood samples for hematology, liver and renal function, and lipids, along with vital signs and interval medical evaluations. When compared with estradiol alone, combinations of drospirenone and estradiol were effective in protecting against endometrial hyperplasia. The probability of hyperplasia was 0.060 (95% CI, 0.043-0.078) for the E(2) monotherapy group, 0.007 for the 2-mg DRSP/E(2) group, and nonsignificant for the remaining drospirenone/estradiol groups. Endometrial bleeding decreased in all treatment groups over time. The combination of drospirenone and E(2) relieved menopausal symptoms and resulted in improvements in health-related quality-of-life measures. There were no significant adverse events, and effects on triglycerides, total cholesterol, and high-density lipoprotein cholesterol were positive. The use of drospirenone combined with estradiol provides protection against endometrial hyperplasia, reduces endometrial bleeding with time, and relieves menopausal symptoms. There were no safety issues and blood pressure was reduced in women with hypertension.


Evolution and use of a note classification scheme in an electronic medical record.
Titles of clinical notes within an electronic medical record (EMR) are important because they influence the speed and completeness of the review of a patient's health record. We created a note classification scheme for notes in our EMR consisting of a 2 level hierarchy of note titles used to identify newly created and existing text and scanned notes. In a sample of 3 of the 18 months since beginning production use, an average of 2,810 notes are added each day. The number of distinct note titles rose by 32 percent between November 2003 and February 2005. Few changes were made to the upper level of the hierarchy. Thirty-three note titles accounted for 75% of the notes entered in February 2005. Note titles are one of several attributes that in conjunction with the user interface used to display them may affect the efficiency and completeness with which clinicians review their patient's records.


A key enzyme for flavin synthesis is required for nitric oxide and reactive oxygen species production in disease resistance.
Nitric oxide (NO) and reactive oxygen species (ROS) play key roles in plant immunity. However, the regulatory mechanisms of the production of these radicals are not fully understood. Hypersensitive response (HR) cell death requires the simultaneous and balanced production of NO and ROS. In this study we indentified NbRibAencoding a bifunctional enzyme, guanosine triphosphate cyclohydrolase II/3,4-dihydroxy-2-butanone-4-phosphate synthase, which participates in the biosynthesis of flavin, by screening genes related to mitogen-activated protein kinase-mediated cell death, using virus-induced gene silencing. Levels of endogenous riboflavin and its derivatives, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are important prosthetic groups for several enzymes participating in redox reactions, decreased in NbRibA-silenced Nicotiana benthamiana. Silencing NbRibA compromised not only HR cell death, but also the NO and ROS production induced by INF1 elicitin and a constitutively active form of NbMEK2 (NbMEK2DD), and also induced high susceptibility to oomycete Phytophthora infestans and ascomycete Colletotrichum orbiculare. Compromised radical production and HR cell death induced by INF1 in NbRibA-silenced leaves were rescued by adding riboflavin, FMN or FAD. These results indicate that flavin biosynthesis participates in regulating NO and ROS production, and HR cell death.


Gene-set association and epistatic analyses reveal complex gene interaction networks affecting flowering time in a worldwide barley collection.
Single-marker genome-wide association studies (GWAS) have successfully detected associations between single nucleotide polymorphisms (SNPs) and agronomic traits such as flowering time and grain yield in barley. However, the analysis of individual SNPs can only account for a small proportion of genetic variation, and can only provide limited knowledge on gene network interactions. Gene-based GWAS approaches provide enormous opportunity both to combine genetic information and to examine interactions among genetic variants. Here, we revisited a previously published phenotypic and genotypic data set of 895 barley varieties grown in two years at four different field locations in Australia. We employed statistical models to examine gene-phenotype associations, as well as two-way epistasis analyses to increase the capability to find novel genes that have significant roles in controlling flowering time in barley. Genetic associations were tested between flowering time and corresponding genotypes of 174 putative flowering time-related genes. Gene-phenotype association analysis detected 113 genes associated with flowering time in barley, demonstrating the unprecedented power of gene-based analysis. Subsequent two-way epistasis analysis revealed 19 pairs of gene×gene interactions involved in controlling flowering time. Our study demonstrates that gene-based association approaches can provide higher capacity for future crop improvement to increase crop performance and adaptation to different environments.


The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia.
This review is focused in PI3K's involvement in two widespread mental disorders: Autism and Schizophrenia. A large body of evidence points to synaptic dysfunction as a cause of these diseases, either during the initial phases of brain synaptic circuit's development or later modulating synaptic function and plasticity. Autism related disorders and Schizophrenia are complex genetic conditions in which the identification of gene markers has proved difficult, although the existence of single-gene mutations with a high prevalence in both diseases offers insight into the role of the PI3K signaling pathway. In the brain, components of the PI3K pathway regulate synaptic formation and plasticity; thus, disruption of this pathway leads to synapse dysfunction and pathological behaviors. Here, we recapitulate recent evidences that demonstrate the imbalance of several PI3K elements as leading causes of Autism and Schizophrenia, together with the plausible new pharmacological paths targeting this signaling pathway.


iPoint: an integer programming based algorithm for inferring protein subnetworks.
Large scale screening experiments have become the workhorse of molecular biology, producing data at an ever increasing scale. The interpretation of such data, particularly in the context of a protein interaction network, has the potential to shed light on the molecular pathways underlying the phenotype or the process in question. A host of approaches have been developed in recent years to tackle this reconstruction challenge. These approaches aim to infer a compact subnetwork that connects the genes revealed by the screen while optimizing local (individual path lengths) or global (likelihood) aspects of the subnetwork. Yosef et al. [Mol. Syst. Biol., 2009, 5, 248] were the first to provide a joint optimization of both criteria, albeit approximate in nature. Here we devise an integer linear programming formulation for the joint optimization problem, allowing us to solve it to optimality in minutes on current networks. We apply our algorithm, iPoint, to various data sets in yeast and human and evaluate its performance against state-of-the-art algorithms. We show that iPoint attains very compact and accurate solutions that outperform previous network inference algorithms with respect to their local and global attributes, their consistency across multiple experiments targeting the same pathway, and their agreement with current biological knowledge.


Antibacterial activity of liposome-entrapped ampicillin in vitro and in vivo in relation to the lipid composition.
The antibacterial activity of liposome-entrapped ampicillin against Listeria monocytogenes was investigated in relation to the lipid composition of the liposomes. This was studied in vitro in mouse peritoneal macrophages infected with L. monocytogenes, as well as in vivo in experimental L. monocytogenes infection in mice. Two types of liposomes, a relatively fluid type, consisting of cholesterol-phosphatidylcholine-phosphatidylserine (5:4:1), and a less fluid type, consisting of cholesterol-distearoylphosphatidylcholine-dipalmitoylphosphatidylglyc erol (10:10:1), were used. The uptake of both types of liposomes by macrophages in vitro was similar. However, the rate of intracellular degradation appeared to be dependent on the lipid composition. A correlation was found between the relatively slow degradation of the less fluid liposomes and a delayed intracellular release of the encapsulated ampicillin, as reflected in absent or delayed intracellular killing of L. monocytogenes in vitro. The results obtained in vitro were confirmed by the observations in vivo. Slow degradation of the less fluid liposomes in vivo resulted in a decrease in the therapeutic effect of the antibiotic.


An open source autocorrelation-based method for fetal heart rate estimation from one-dimensional Doppler ultrasound.
Open research on fetal heart rate (FHR) estimation is relatively rare, and evidence for the utility of metrics derived from Doppler ultrasound devices has historically remained hidden in the proprietary documentation of commercial entities, thereby inhibiting its assessment and improvement. Nevertheless, recent studies have attempted to improve FHR estimation; however, these methods were developed and tested using datasets composed of few subjects and are therefore unlikely to be generalizable on a population level. The work presented here introduces a reproducible and generalizable autocorrelation (AC)-based method for FHR estimation from one-dimensional Doppler ultrasound (1D-DUS) signals. Simultaneous fetal electrocardiogram (fECG) and 1D-DUS signals generated by a hand-held Doppler transducer in a fixed position were captured by trained healthcare workers in a European hospital. The fECG QRS complexes were identified using a previously published fECG extraction algorithm and were then over-read to ensure accuracy. An AC-based method to estimate FHR was then developed on this data, using a total of 721 1D-DUS segments, each 3.75 s long, and parameters were tuned with Bayesian optimization. The trained FHR estimator was tested on two additional (independent) hand-annotated Doppler-only datasets recorded with the same device but on different populations: one composed of 3938 segments (from 99 fetuses) acquired in rural Guatemala, and another composed of 894 segments (from 17 fetuses) recorded in a hospital in the UK. The proposed AC-based method was able to estimate FHR within 10% of the reference FHR values 96% of the time, with an accuracy of 97% for manually identified good quality segments in both of the independent test sets. This is the first work to publish open source code for FHR estimation from 1D-DUS data. The method was shown to satisfy estimations within 10% of the reference FHR values and it therefore defines a minimum accuracy for the field to match or surpass. Our work establishes a basis from which future methods can be developed to more accurately estimate FHR variability for assessing fetal wellbeing from 1D-DUS signals.


Pharmacy and medical claims data identified migraine sufferers with high specificity but modest sensitivity.
Claims data are often used to identify and monitor individuals with particular conditions, but many health conditions are not easily recognizable from claims data alone. Patient characteristics routinely available in claims data were used to develop model-based claims signatures to identify migraineurs. A validated telephone interview was administered to 23,299 continuously enrolled managed care members aged 18-55 to identify 1,265 migraineurs and 1,178 controls. Responses were linked to medical and prescription claims. Claims variables were evaluated for sensitivity, specificity, and positive and negative predictive value in predicting migraine status. Regression models for predicting migraine status were developed. Regression-based claims signature models were successful in case-finding, as indicated by fairly sizable odds ratios (OR). In the full model (including demographic, medical, pharmacy, and comorbidity claims variables), a claim for a migraine drug, gender, and a claims-based headache diagnosis were strongly associated with migraine case status (OR=3.9, 3.2, and 3.0, respectively). Using either medical or pharmacy claims provided highly specific and moderately sensitive case-findings. Strategies that combined medical and pharmacy information improved sensitivity and may increase the usefulness of claims for identifying migraine and improving the quality of migraine care.


Machine Learning for Automatic Encoding of French Electronic Medical Records: Is More Data Better?
The encoding of Electronic Medical Records is a complex and time-consuming task. We report on a machine learning model for proposing diagnoses and procedures codes, from a large realistic dataset of 245 000 electronic medical records at the University Hospitals of Geneva. Our study particularly focuses on the impact of training data quantity on the model's performances. We show that the performances of the models do not increase while encoded instances from previous years are exploited for learning data. Furthermore, supervised models are shown to be highly perishable: we show a potential drop in performances of around -10% per year. Consequently, great and constant care must be exercised for designing and updating the content of such knowledge bases exploited by machine learning.


Probiotics for treating acute infectious diarrhoea.
Probiotics may be effective in reducing the duration of acute infectious diarrhoea. To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. We searched the trials register of the Cochrane Infectious Diseases Group, MEDLINE, and Embase from inception to 17 December 2019, as well as the Cochrane Controlled Trials Register (Issue 12, 2019), in the Cochrane Library, and reference lists from studies and reviews. We included additional studies identified during external review. Randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data. Primary outcomes were measures of diarrhoea duration (diarrhoea lasting ≥ 48 hours; duration of diarrhoea). Secondary outcomes were number of people hospitalized in community studies, duration of hospitalization in inpatient studies, diarrhoea lasting ≥ 14 days, and adverse events. We included 82 studies with a total of 12,127 participants. These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group). No cluster-randomized trials were included. Studies varied in the definitions used for "acute diarrhoea" and "end of the diarrhoeal illness" and in the probiotic(s) tested. A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high. Risk of bias was high or unclear in many studies, and there was marked statistical heterogeneity when findings for the primary outcomes were pooled in meta-analysis. Effect size was similar in the sensitivity analysis and marked heterogeneity persisted. Publication bias was demonstrated from funnel plots for the main outcomes. In our main analysis of the primary outcomes in studies at low risk for all indices of risk of bias, no difference was detected between probiotic and control groups for the risk of diarrhoea lasting ≥ 48 hours (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.91 to 1.09; 2 trials, 1770 participants; moderate-certainty evidence); or for duration of diarrhoea (mean difference (MD) 8.64 hours shorter, 95% CI 29.4 hours shorter to 12.1 hours longer; 6 trials, 3058 participants; very low-certainty evidence). Effect size was similar and marked heterogeneity persisted in pre-specified subgroup analyses of the primary outcomes that included all studies. These included analyses limited to the probiotics Lactobacillus rhamnosus GG and Saccharomyces boulardii. In six trials (433 participants) of Lactobacillus reuteri, there was consistency amongst findings (I² = 0%), but risk of bias was present in all included studies. Heterogeneity also was not explained by types of participants (age, nutritional/socioeconomic status captured by mortality stratum, region of the world where studies were undertaken), diarrhoea in children caused by rotavirus, exposure to antibiotics, and the few studies of children who were also treated with zinc. In addition, there were no clear differences in effect size for the primary outcomes in post hoc analyses according to decade of publication of studies and whether or not trials had been registered. For other outcomes, the duration of hospitalization in inpatient studies on average was shorter in probiotic groups than in control groups but there was marked heterogeneity between studies (I² = 96%; MD -18.03 hours, 95% CI -27.28 to -8.78, random-effects model: 24 trials, 4056 participants). No differences were detected between probiotic and control groups in the number of people with diarrhoea lasting ≥ 14 days (RR 0.49, 95% CI 0.16 to 1.53; 9 studies, 2928 participants) or in risk of hospitalization in community studies (RR 1.26, 95% CI 0.84 to 1.89; 6 studies, 2283 participants). No serious adverse events were attributed to probiotics. Probiotics probably make little or no difference to the number of people who have diarrhoea lasting 48 hours or longer, and we are uncertain whether probiotics reduce the duration of diarrhoea. This analysis is based on large trials with low risk of bias.


Sarcoid-like reaction in the regional lymph nodes and spleen in gastric carcinoma: a clinicopathologic study of five cases.
To clarify the occurrence of sarcoid-like reaction in the spleen of the gastric carcinoma patients, 100 consecutive specimens from gastrosplenectomy were examined. Sarcoid-like reaction was observed in the lymph nodes of 13 cases (13%) and the spleen of five cases (5%). All cases of the latter group were included in the former one. None of them showed any symptoms or signs indicative of systemic sarcoidosis. It seems that the cases with sarcoid-like reaction in the spleen ocurred more frequently in an advanced stage of the gastric cancer than those without this phenomenon. Epithelioid cell granulomas (EPGs) appeared to arise in the periarteriolar lymphoid sheaths of the spleen histologically, but were never found in red pulp or germinal centers. They were composed of groups of epithelioid cells and accompanied by the small lymphocytes and plasma cells. In three cases, scattered eosinophils were also observed among the epithelioid cells. Immunohistochemically, the majority of the intragranulomatous small lymphocytes had T-cell phenotype, while B-cells formed only the minor cellular population. None of the 13 cases contained EPGs in the primary tumor. Our study indicates that sarcoid-like reaction in the spleen is possibly not such a rare phenomenon in the gastric cancer as previously considered and more frequently seen in the advanced stage of the gastric cancer. Sarcoid-like reactions of the regional lymph nodes were more frequently seen in the patients with EPGs in the spleen than in those without. We also suggest that the incidence of sarcoid-like reactions in the spleen is closely related to those in pancreaticosplenic nodes and/or nodes of the hilus of the spleen.


EVALUATION OF ANTICANCER POTENTIAL OF EIGHT VEGETAL SPECIES FROM THE STATE OF OAXACA.
Eight plant species from Oaxaca, some of them used in traditional medicine, were subjected to screening of several biological activities to provide data regarding their anticancer potential, although no scientific information is available about their pharmacological effects. Methanol extracts from stems or roots of the eight plants were tested for antioxidant activity by the DPPH- method. Antimicrobial activity was determined using the agar diffusion method and the minimal inhibitory concentration (MIC) was obtained by broth dilution method. Antitopoisomerase activity was assessed using mutant strains of Saccharomyces cerevisiae JN362a, JN394, JN394t-1, JN394t2.4 and JN394t2-5. The mutagenic activity was evaluated using the Ames test (Salmonella typhimurium TA1535). No extract showed significant antioxidant activity. The best antimicrobial activity was observed for Salpianthus arenarius (MIC 56.25 μg/mL) and Lantana achyranthifolia (MIC 78.12 μg/mL) against Staphylococcus aureus. Extracts of Acalypha cuspidata, Alloispermum integrifolium and L. achyranthifolia stems showed antitopoisomerase II activity with JN394t-1 growth of -30.88±0.0%, -38.11±4.95%, and -70.97±12.02% respectively. Galium mexicanum stem extract showed antitopoisomerase I activity with growth of 35.31±6.36% on the same mutant strain. All plant extracts were non-mutagenic. Fractionation of A. cuspidata extract led to identification of two subfractions with antitopoisomerase I and II activity at 154μg/mL (Positive controls 50 and 100μg/mL). Methanol extracts of A. cuspidata, A. integrifolium, G. mexicanum, and L. achyranthifolia stems showed antitopoisomerase and non-mutagenic activities, and consequently could be promising as a source of anticancer drugs.


Protein quality in cereals and pulses. 1. Application of microbiological and other in vitro methods in the evaluation of rice (Oryza sativa L.), sorghum (Sorghum vulgare Pers.), barley and field beans (Vicia faba L.).
1. The Streptococcus zymogenes assay procedure was modified and used in the estimation of available methionine and relative nutritional value in rice (Oryza sativa L.), sorghum (Sorghum vulgare Pers.), barley and field beans (Vicia faba L.). The results were assessed in relation to the content of tannins and 'dye-binding lysine', and to published information on the nutritional quality of some of the test samples. 2. In grain of ten varieties of sorghum, for which other workers had reported a correlation (r -0.82; P less than 0.01) between tannin content and amino acid digestibility in chicks, the available methionine content ranged from 6.3 to 17.7 g/kg protein (nitrogen x 6.25) and was highly correlated with tannin content (r -0.97; P less than 0.001). The content of total methionine and dye-binding lysine varied little between varieties and was not related to tannin content. 3. In nine samples of rice the availability of methionine was uniformly high, in accordance with literature values for true digestibility of the N. 4. In field beans the presence of tammins in the seed coat was associated with a significant (P less than 0.001) reduction in the availability of methionine. In eleven tannin-free varieties the coefficient of availability averaged 0.791, compared with 0.685 in eleven tannin-containing varieties. The standard deviation associated with both values was 0.04. There was no such difference between the corresponding dye-binding lysine values. 5. Thirty-three samples of barley were examined, representing fourteen varieties, four of which had been grown at several widely different latitudes in England and Sweden. There was little difference in methionine content between samples. The average availability coefficient for eighteen samples grown in England was 0.995+/-0.044, and for fifteen varieties grown in Sweden it was 0.851+/-0.042. The difference was not associated with any difference in tannin content, which was uniformly low. The findings contradict published evidence for marked increase in tannin content with increase in geographical latitude of cultivation, associated with decrease in digestibility of N.


[State strategy for Cycad (Zamiaceae) conservation: a proposal for the State of Hidalgo, Mexico].
Mexico has the second largest cycad diversity in the world, and the Sierra Madre Oriental (SMO) is one of the richest biogeographic regions for these plants. Despite there is a general Cycad National Program in the country, there are no state-level cycad conservation strategies or programs. Thus the aim of this study was to propose a cycad conservation strategy for the state of Hidalgo, which is located in the Southern part of the SMO. For this, a cycad species inventory was made in the state, for which three methods were used: review of published literature; consultation in the main Mexican herbaria to verify botanical specimens; and exhaustive field research to compare findings with previously reported species and to recognize new records at the county and state level. The proposed research work strategy combined the following elements: prioritize the county and local areas with greatest cycad species richness; prioritize the species least resistant to environmental change and/or having restricted geographic distribution; and to consider the main uses of these plants by local residents. The results showed that Hidalgo has three genera and eight species ofcycads: Ceratozamia fuscoviridis, C. latifolia, C. mexicana, C. sabatoi, Dioon edule, Zamia fischeri, Z. loddigesii and Z. vazquezii, all of which are considered by the International Union for Conservation of Nature (IUCN). This study added two new species records for Hidalgo and 21 at the county level. The species are distributed in 26 counties, of which Chapulhuacán and Pisaflores are notable for their high species richness. Hidalgo has the fourth-greatest cycad species richness among Mexican states, although its area accounts for only 1.07% of the country. The state's diversity is greater than in other states with larger area, and even than in some other entire countries in Mesoamerica. The presented state cycad conservation strategy proposes that a total of some 11,325 ha to be conserved in nine zones, including different vegetation types, distributed in seven counties. The strategy involves a mixed scheme that incorporates conservation in Protected Natural Areas (ANP), Small Farmer Reserves (Reservas Campesinas) and Environmental Management Units (UMA in Spanish). This proposal will be useful for government agencies to take into account in the process of designating land use for the Cloud Forest Biological Corridor (CBBMM in Spanish), a ANP in creation. The state of Hidalgo urgently needs a detailed analysis of trends in changes in vegetation cover and land use, and demographic studies of the cycads. It is recommended that the implementation phase of this state strategy be carried out jointly with local communities, academia, and state and federal agencies responsible for biodiversity conservation.


Flow-sensitive four-dimensional velocity-encoded magnetic resonance imaging reveals abnormal blood flow patterns in the aorta and pulmonary trunk of patients with transposition.
Flow profiles are important determinants of fluid-vessel wall interactions. The aim of this study was to assess blood flow profiles in the aorta and pulmonary trunk in patients with transposition and different ventriculoarterial connection, and hence different mechanics of the coherent pump. In all, 29 patients with operated transposition--concordant atrioventricular and discordant ventriculoarterial connection, and no other cardiac malformation--and eight healthy volunteers were assessed with cardiac magnetic resonance imaging: n = 17 patients after atrial redirection, with a morphologic right ventricle acting as systemic pump and a morphologic left ventricle connected to the pulmonary trunk, and n = 12 patients after the arterial switch procedure, with physiologic ventriculoarterial connections. Flow-sensitive four-dimensional velocity-encoded magnetic resonance imaging was used to analyse systolic flow patterns in the aorta and pulmonary trunk, relating to helical flow and vortex formation. In the aorta, overall helicity was present in healthy volunteers, but it was absent in all patients independent on the operation technique. Partial helices were observed in the ascending aorta of 58% of patients after arterial switch. In the pulmonary trunk, mostly parallel flow was seen in healthy volunteers and in patients after arterial switch, whereas vortex formation was present in 88% of patients after atrial redirection. Blood flow patterns differ substantially between the groups. In addition to varying mechanics of the coherent pumping ventricles, the absent overall helicity in all patients might be explained by the missing looping of the aorta in transposition.


Description and validation of the ActiReg: a novel instrument to measure physical activity and energy expenditure.
The ActiReg (PreMed AS, Oslo, Norway) system is unique in using combined recordings of body position and motion alone or combined with heart rate (HR) to calculate energy expenditure (EE) and express physical activity (PA). The ActiReg has two pairs of position and motion sensors connected by cables to a battery-operated storage unit fixed to a waist belt. Each pair of sensors was attached by medical tape to the chest and to the front of the right thigh respectively. The collected data were transferred to a personal computer and processed by a dedicated program ActiCalc. Calculation models for EE with and without HR are presented. The models were based on literature values for the energy costs of different activities and therefore require no calibration experiments. The ActiReg system was validated against doubly labelled water (DLW) and indirect calorimetry. The DLW validation demonstrated that neither EE calculated from ActiReg data alone (EEAR) nor from combined ActiReg and HR data (EEAR-HR) were statistically different from DLW results. The EEAR procedure causes some underestimation of EE >11 MJ corresponding to a PA level >2.0. This underestimation is reduced by the EEAR-HR procedure. The objective recording of the time spent in different body positions and at different levels of PA may be useful in studies of PA in different groups and in studies of whether recommendations for PA are being met. The comparative ease of data collection and calculation should make ActiReg a useful instrument to measure habitual PA level and EE.


Systems cell biology knowledge created from high content screening.
High content screening (HCS), the large-scale automated analysis of the temporal and spatial changes in cells and cell constituents in arrays of cells, has the potential to create enormous systems cell biology knowledge bases. HCS is being employed along with the continuum of the early drug discovery process, including lead optimization where new knowledge is being used to facilitate the decision-making process. We demonstrate methodology to build new systems cell biology knowledge using a multiplexed HCS assay, designed with the aid of knowledge-mining tools, to measure the phenotypic response of a panel of human tumor cell types to a panel of natural product-derived microtubule-targeted anticancer agents and their synthetic analogs. We show how this new systems cell biology knowledge can be used to design a lead compound optimization strategy for at least two members of the panel, (-)-laulimalide and (+)-discodermolide, that exploits cell killing activity while minimally perturbing the regulation of the cell cycle and the stability of microtubules. Furthermore, this methodology can also be applied to basic biomedical research on cells.


THE LS-ANTIGEN OF VACCINIA : IV. CHEMICAL ANALYSIS OF LS AND THE EFFECT OF CHYMOTRYPSIN ON LS.
Pure LS-antigen of vaccinia contains 15.8 per cent N and 50.6 per cent C. These analytical data together with the absence of lipids, phosphorus, nucleic acid, and glucosamine in preparations of the antigen confirm the protein nature of the substance. The action of proteolytic enzymes on LS offers further confirmation of the protein character of the antigen. Both the L- and S-activities of the antigen are destroyed by digestion with papain. The effects of crystalline chymotrypsin on LS-antigen are particularly interesting for, under proper conditions, this enzyme destroys the serological activity of the S-portion of the molecule without affecting the L-portion. This newly prepared degradation product of LS, called LS'', contains the same amount of N as the native substance but unlike LS, it forms needle-shaped crystalloids.


Conformational dynamics of the trp-cage miniprotein at its folding temperature.
The folding temperature of the trp-cage mini-protein was determined to be in the range 311-317 K depending on the method used. Our study is focused on determining the structure and dynamics of the polypeptide chain close to its unfolding or melting temperature. At T = 305 K, Trp6-Arg16 and Trp6-Pro12 long-range interactions are observed, and at T = 313 K, only the Trp6-Arg16 interactions remain, while all of mentioned interactions are observed in the native state of the protein. Partial (at T = 305 K) and complete (at T = 313 K) melting of the N-terminal α-helix is observed, manifested by the appearance of minor sets of signals in NMR spectra. Our key findings are: (i) conformational phase transition (melting point) could be described as a cooperative breaking of the Trp6-Pro12 long-range hydrophobic interaction and the melting of the N-terminal α-helix; (ii) many ROE signals corresponding to local or short-range interactions vanish rapidly with temperature increase; however, long-range interaction such as Trp6-Arg16 remains until 313 K. The presence of the native long-range interaction at 313 K makes that conformational ensemble resemble a very diffuse native state structure, but it is not a simple mixture of the folded and unfolded states, as could be expected on the basis of the common two-state folding mechanism.


Rubella susceptibility in Navajo women.
Rubella susceptibility among Navajo women equals that in other parts of the country. Even though crowded conditions exist in the homes, communicable disease is more prevalent than in other areas, and many children attend boarding schools. The present immunization policy is discussed and an alternative plan of immunization is presented as recently recommended by the Navajo Area Indian Health service committee on rubella.


Color and power Doppler ultrasonography for characterization of splenic masses in dogs.
Benign and malignant splenic masses can appear similar on B-mode imaging, making ultrasound sensitive but not specific in their diagnosis. Our goal was to characterize color and/or power Doppler characteristics of vasculature within and adjacent to a splenic mass, which would distinguish benign vs. malignant lesions. The hypothesis was that malignant splenic masses will have altered vascular patterns compared with benign masses. Color and power Doppler cineloops evaluating the vasculature within the mass and normal splenic parenchyma were obtained in sagittal and transverse planes using a standardized protocol. Categories of evaluation included presence of peritoneal effusion, a large aberrant or tortuous vessel within the mass, relative blood flow within the mass compared with normal parenchyma, and path of vessels in the adjacent parenchyma entering into the mass. All patients had histopathologic or definitive cytologic diagnosis. Thirty-one dogs were included. There were 13 malignant masses and 18 were benign. Peritoneal effusion was significantly associated with malignancy (P = 0.0007). Presence of an aberrant or tortuous vessel within the mass was nearly significant (P = 0.059). There was no significant difference in any of the color or power Doppler blood flow evaluations. Ultrasonographic findings of a splenic mass and peritoneal effusion may indicate malignancy. The presence of an aberrant vessel within a splenic mass could suggest malignancy; however more data are needed.


KISS1 metastasis suppression and emergent pathways.
Metastatic disease is the most critical impediment to cancer patient survival. However, comparatively little is known concerning the intricate pathways which govern the complex phenotypes associated with metastasis. The KISS1 metastasis suppressor gene inhibits metastasis in both in vivo melanoma and breast carcinoma models. Despite its clear physiological activity, the mechanism of KISS1 remains unclear. Recent identification of a 54 amino acid peptide of KISS1, termed metastin or kisspeptin-54, and its cognate G-protein coupled receptor (hOT7T175, AXOR12, GPR54) have provided additional clues and avenues of research. While studies have attributed KISS1 with modulation of NFkappaB regulation, experiments with metastin and its receptor implicate MAP kinase pathways and also suggest the potential of autocrine, paracrine and endocrine roles. Impacts on motility, chemotaxis, adhesion and invasion have each been documented in disparate cell lines and conflicting observations require resolution. Nevertheless, mounting clinical evidence, particularly the loss of KISS1 in metastases, correlates KISS1 and metastin receptor expression with human tumor progression. Together, the data substantiate roles for these molecules in metastasis regulation.


Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats.
Cannabidiol (CBD) is a cannabinoid component from Cannabis sativa that does not induce psychotomimetic effects and possess anti-inflammatory properties. In the present study we tested the effects of CBD in a periodontitis experimental model in rats. We also investigated possible mechanisms underlying these effects. Periodontal disease was induced by a ligature placed around the mandible first molars of each animal. Male Wistar rats were divided into 3 groups: control animals; ligature-induced animals treated with vehicle and ligature-induced animals treated with CBD (5 mg/kg, daily). Thirty days after the induction of periodontal disease the animals were sacrificed and mandibles and gingival tissues removed for further analysis. Morphometrical analysis of alveolar bone loss demonstrated that CBD-treated animals presented a decreased alveolar bone loss and a lower expression of the activator of nuclear factor-kappaB ligand RANKL/RANK. Moreover, gingival tissues from the CBD-treated group showed decreased neutrophil migration (MPO assay) associated with lower interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha production. These results indicate that CBD may be useful to control bone resorption during progression of experimental periodontitis in rats.


Separate mechanisms for number reading and word reading: Evidence from selective impairments.
Do number reading and word reading use the same cognitive mechanisms? We examined this question through the looking glass of dissociations between impairments in number and word reading. We report two women with selective deficits in number reading, who read words normally. An examination of their impairment pattern indicated that the specific locus of their number reading deficits is in processes that handle the number's structure: both were impaired in parsing a digit string into triplets, and one of them was also impaired in generating the number's verbal structure. In contrast to their structural deficits in number reading, their word reading was completely intact, including the structural processes in word reading (morphological analysis and assembly). We present this dissociation in the framework of a broader effort to examine dissociations between specific components in number and word reading. We went beyond general word-number dissociations: we used detailed cognitive models for word reading and for number reading, and analyzed them in order to identify which components of the number reading process are homologous to which components of words reading. We then show that even these homologous processes are dissociable: an examination of previously-reported dissociations, completed by the case studies presented here, indicated that each of the specific homologous sub-processes of word/number reading can be selectively impaired. We conclude that although the word and number reading pathways show much similarity, they are almost entirely separate.


Target-induced nanocatalyst deactivation facilitated by core@shell nanostructures for signal-amplified headspace-colorimetric assay of dissolved hydrogen sulfide.
Colorimetric assay platforms for dissolved hydrogen sulfide (H2S) have been developed for more than 100 years, but most still suffer from relatively low sensitivity. One promising route out of this predicament relies on the design of efficient signal amplification methods. Herein, we rationally designed an unprecedented H2S-induced deactivation of (gold core)@(ultrathin platinum shell) nanocatalysts (Au@TPt-NCs) as a highly efficient signal amplification method for ultrasensitive headspace-colorimetric assay of dissolved H2S. Upon target introduction, Au@TPt-NCs were deactivated to different degrees dependent on H2S levels, and the degrees could be indicated by using a Au@TPt-NCs-triggered catalytic system as a signal amplifier, thus paving a way for H2S sensing. The combination of experimental studies and density functional theory (DFT) studies revealed that the Au@TPt-NCs with only 2-monolayer equivalents of Pt (θPt = 2) were superior for H2S-induced nanocatalyst deactivation owing to their enhanced peroxidase-like catalytic activity and deactivation efficiency stemmed from the unique synergistic structural/electronic effects between Au nanocores and ultrathin Pt nanoshells. Importantly, our analytical results showed that the designed method was indeed highly sensitive for sensing H2S with a wide linear range of 10-100 nM, a slope of 0.013 in the regression equation, and a low detection limit of 7.5 nM. Also the selectivity, reproducibility, and precision were excellent. Furthermore, the method was validated for the analysis of H2S-spiked real samples, and the recovery in all cases was 91.6-106.7%. With the merits of high sensitivity and selectivity, simplification, low cost, and visual readout with the naked eye, the colorimetric method has the potential to be utilized as an effective detection kit for point-of-care testing.


Migratory dental implant in the maxillary antrum: a case report.
Dental implants offer a predictable solution for the replacement of missing dentition. This report describes the case of a patient who underwent dental implant surgery several years ago but due to negligence on the part of previous dentist, her implant pushed into the maxillary sinus. The patient presented with vague pain and swelling in the right maxillary region. Orthopantomogram (OPG) showed that the implant was lying in the right maxillary sinus which the patient had no clue of. It was decided to retrieve the implant and later restore the missing teeth for definitive function and aesthetics. However, at the time of surgery, the implant in question was missing from the anticipated position as it had migrated to the most posterior-superior compartment of the antrum making its retrieval difficult in the first attempt. Later, a maxillofacial surgeon carried out the retrieval. Fortunately, the implant moved back to a more favourable position at the time of second surgery.


The use of depot neuroleptics: clinical experience in the United States.
The use of long-acting injectable preparations such as fluphenazine enanthate or decanoate can reduce patient noncompliance, but documenting this in a controlled research design is difficult. Several studies of relapse rates among patients receiving oral fluphenazine, depot fluphenazine, or placebo are reviewed. Factors that may explain the lack of significant differences among different drug treatments in preventing relapse are discussed. Indications are presented for the use of depot neuroleptics, and strategies for achieving minimum effective doses are reviewed. Adverse effects of depot medication are also discussed, so that the clinician may maximize the ratio of benefit to risk.


Coping with Tinnitus: Two Studies of Psychological and Audiological Characteristics of Patients with High and Low Tinnitus-Related Distress.
Two studies are described which were designed to investigate the relationship between psychological distress and tinnitus. In the first study, four groups of subjects (N=72) who differed in degree of tinnitus-related distress were compared on audiological measures. No differences were found between the four groups on loudness, pitch and minimum masking level when employing the Bonferroni correction which controls for inflation of the Type I error rate when conducting multiple statistical tests on the same set of data. The univariate tests indicated that the more severely distressed tinnitus sufferers experienced loud tinnitus as measured by a loudness match procedure. In the second study, 81 tinnitus patients were categorised as either displaying high or low tinnitus-related distress. The two groups were compared on various measures including level of depressive symptomatology, reported use of coping strategies, perceived benefits from these coping strategies, reported engagement in depression-related negative cognitions, and tinnitus-specific dysfunctioning thinking. High distress subjects were found to have elevated scores on the Beck Depression Inventory. These subjects also reported engaging in more dysfunctional thinking specifically in relation to tinnitus. The implications of the findings of the two studies are discussed.


Difference in performance between 3D and 4D CBCT for lung imaging: a dose and image quality analysis.
The study was to describe and to compare the performance of 3D and 4D CBCT imaging modalities by measuring and analyzing the delivered dose and the image quality. The 3D (Chest) and 4D (Symmetry) CBCT Elekta XVI lung IGRT protocols were analyzed. Dose profiles were measured with TLDs inside a dedicated phantom. The dosimetric indicator cone-beam dose index (CBDI) was evaluated. The image quality analysis was performed by assessing the contrast transfer function (CTF), the noise power spectrum (NPS) and the noise-equivalent quanta (NEQ). Artifacts were also evaluated by simulating irregular breathing variations. The two imaging modalities showed different dose distributions within the phantom. At the center, the 3D CBCT delivered twice the dose of the 4D CBCT. The CTF was strongly reduced by motion compared to static conditions, resulting in a CTF reduction of 85% for the 3D CBCT and 65% for the 4D CBCT. The amplitude of the NPS was two times higher for the 4D CBCT than for the 3D CBCT. In the presence of motion, the NEQ of the 4D CBCT was 50% higher than the 3D CBCT. In the presence of breathing irregularities, the 4D CBCT protocol was mainly affected by view-aliasing artifacts, which were typically cone-beam artifacts, while the 3D CBCT protocol was mainly affected by duplication artifacts. The results showed that the 4D CBCT ensures a reasonable dose and better image quality when mov-ing targets are involved compared to 3D CBCT. Therefore, 4D CBCT is a reliable imaging modality for lung free-breathing radiation therapy.


Body composition during the first 4 months in infants affected by neonatal abstinence syndrome: a pilot study.
Newborns with neonatal abstinence syndrome (NAS) display symptoms related to neurologic excitability and autonomic dysfunction that result in increased metabolic demands. These infants also exhibit feeding difficulties and/or hyperphagia. Because the effects of these symptoms and behaviors on growth are unknown, we sought to measure serial body composition measurements over the first 4 months in infants with NAS requiring pharmacologic treatment using air displacement plethysmography. Fourteen infants of singleton birth with appropriate-for-gestational-age (AGA) weight and a gestational age of ≥35 weeks and <42 weeks were evaluated. In mixed-effects models, per week, infants increased in mean fat percent by 1.1% (95% confidence interval [CI]: 0.85-1.43), fat mass by 90 g (CI: 70-100), and fat-free mass by 140 g (CI: 130-150). The subgroup of infants (N = 5) requiring multidrug therapy for symptom control had lower mean fat percent (-1.2%, CI: -5.2-2.1), fat mass (-60 g, CI: -25-13), and fat-free mass (-270 g, CI: -610-80) across time compared to infants requiring monotherapy. We are the first to report how body composition measures change over time in a small group of patients with NAS. Infants with NAS were smaller and leaner in the first several weeks compared to previously reported body composition measurements in term infants, but grew similarly to their healthy counterparts by 16 weeks. Infants with more severe NAS may be at risk for abnormalities in longer term growth.


Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake.
Studies have shown decreased cerebral oxygen metabolism (CMRO(2)) and blood flow (CBF) in patients with cirrhosis with hepatic encephalopathy (HE). It remains unclear, however, whether these disturbances are associated with HE or with cirrhosis itself and how they may relate to arterial blood ammonia concentration and cerebral metabolic rate of blood ammonia (CMRA). We addressed these questions in a paired study design by investigating patients with cirrhosis during and after recovery from an acute episode of HE type C. CMRO(2), CBF, and CMRA were measured by dynamic positron emission tomography (PET)/computed tomography (CT). Ten patients with cirrhosis were studied during an acute episode of HE; nine were reexamined after recovery. Nine patients with cirrhosis with no history of HE served as controls. Mean CMRO(2) increased from 0.73 μmol oxygen/mL brain tissue/min during HE to 0.91 μmol oxygen/mL brain tissue/min after recovery (paired t test; P < 0.05). Mean CBF increased from 0.28 mL blood/mL brain tissue/min during HE to 0.38 mL blood/mL brain tissue/min after recovery (P < 0.05). After recovery from HE, CMRO(2) and CBF were not significantly different from values in the control patients. Arterial blood ammonia concentration decreased 20% after recovery (P < 0.05) and CMRA was unchanged (P > 0.30); both values were higher than in the control patients (both P < 0.05). The low values of CMRO(2) and CBF observed during HE increased after recovery from HE and were thus associated with HE rather than the liver disease as such. The changes in CMRO(2) and CBF could not be linked to blood ammonia concentration or CMRA.


Perioperative hospital mortality at a tertiary paediatric institution.
Research in postoperative mortality is scarce. Insight into mortality and cause of death might improve and innovate perioperative care. The objective for this study was to report the 24-hour and 30-day overall, and surgery and anaesthesia-related, in-hospital mortality at a tertiary paediatric hospital. All patients <18 yr old who underwent anaesthesia with or without surgery between January 1, 2006, and December 31, 2012, at the Wilhelmina Children's Hospital, Utrecht, The Netherlands, were included in this retrospective cohort study. Causes of death within 30 days were identified and tabulated into four major categories according to principal cause. A total of 45,182 anaesthetics were administered during this 7-yr period. The all-cause 24-hour hospital mortality was 13.1 per 10,000 anaesthetics (95% CI: 9.9-16.8) and the all-cause 30-day in-hospital mortality was 41.6 per 10,000 anaesthetics (95% CI: 35.9-48.0). In total five patients were partially contributable to anaesthesia (30-day mortality: 1.1/10,000, 95% CI: 0.4-2.6) and four patients were partially contributable to surgery (30-day mortality: 0.9/10,000, 95% CI: 0.2-2.3). Mortality was higher in neonates and infants, children with ASA physical status III and IV, and emergency- and cardiothoracic surgery. Neonates and infants, children with ASA physical status III or poorer, and emergency- and cardiothoracic surgery are associated with a higher postoperative mortality. Anaesthesia- or surgery-related complications contribute to mortality in only a small amount of the deaths, indicating the relative safety of paediatric surgical and anaesthetic procedures.


Phospholipid scramblase 1 interacts with influenza A virus NP, impairing its nuclear import and thereby suppressing virus replication.
Transcription and replication of the influenza A virus (IAV) genome occur in the nucleus of infected cells and are carried out by the viral ribonucleoprotein complex (vRNP). As a major component of the vRNP complex, the viral nucleoprotein (NP) mediates the nuclear import of the vRNP complex via its nuclear localization signals (NLSs). Clearly, an effective way for the host to antagonize IAV infection would be by targeting vRNP nuclear import. Here, we identified phospholipid scramblase 1 (PLSCR1) as a binding partner of NP by using a yeast two-hybrid (Y2H) screen. The interaction between NP and PLSCR1 in mammalian cells was demonstrated by using co-immunoprecipitation and pull-down assays. We found that the stable overexpression of PLSCR1 suppressed the nuclear import of NP, hindered the virus life cycle, and significantly inhibited the replication of various influenza subtypes. In contrast, siRNA knockdown or CRISPR/Cas9 knockout of PLSCR1 increased virus propagation. Further analysis indicated that the inhibitory effect of PLSCR1 on the nuclear import of NP was not caused by affecting the phosphorylation status of NP or by stimulating the interferon (IFN) pathways. Instead, PLSCR1 was found to form a trimeric complex with NP and members of the importin α family, which inhibited the incorporation of importin β, a key mediator of the classical nuclear import pathway, into the complex, thus impairing the nuclear import of NP and suppressing virus replication. Our results demonstrate that PLSCR1 negatively regulates virus replication by interacting with NP in the cytoplasm and preventing its nuclear import.


Calcitropic effects of recombinant prolactins in Oreochromis mossambicus.
Homologous recombinant tilapia prolactin-188 (PRL-I) and tilapia prolactin-177 (PRL-II) were tested for calcitropic activity in tilapia, Oreochromis mossambicus. Injection of PRL-I and PRL-II (4 injections, 12.5 pmol/g, over an 8-day period) induced hypercalcemia that resulted from an enhanced calcium influx via the gills and a decreased calcium efflux. Both PRLs increased the density of the Ca(2+)-transporting Ca(2+)-adenosinetriphosphatase in a plasma membrane preparation of the branchial epithelium. Dose-response studies (doses tested: 0.75-12.5 pmol/g) demonstrated that PRL-I was roughly twofold more potent than PRL-II in inducing hypercalcemia, in enhancing basal levels of cortisol, and in stimulating opercular ionocyte density. PRL-I and PRL-II were equipotent in stimulating the dermal mucocyte frequency. We conclude that in this species PRL-I and PRL-II have calcitropic effects, and that PRL-I is more potent than PRL-II in this respect. We postulate that PRL has corticotrophic activity in this fish.


[The role of G-CSF in host defense mechanisms of the elderly].
It has been generally agreed that the elderly had a greater susceptibility, morbidity, and mortality in regard to a variety of bacterial infections. To clarify the host defence mechanism in the elderly, we studied the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophil functions, the production of G-CSF by peripheral blood monocytes in response to lipopolysaccharide (LPS) and the serum levels of G-CSF in patients with bacterial pneumonia. There was no significant difference in the phagocytic activity of neutrophils between the elderly and control young adults. rhG-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both group. Killing activity of neutrophils assessed by the new nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p < 0.001), however, pretreatment with rhG-CSF resulted in an increase of killing activity in the elderly, raising their response to a level compatible to that of young adults pretreated with rhG-CSF. The amount of G-CSF in the culture supernatants from LPS-stimulated peripheral blood monocytes of the elderly was significantly lower than that of young adults (p < 0.05). The serum levels of G-CSF in the acute phase of bacterial pneumonia in the elderly were significantly lower than those of young adults (p < 0.01). These results indicated that impaired monocyte function may contribute, at least in part, to susceptibility to bacterial infection in the elderly.


Transferable plasmid-mediated resistance to linezolid due to cfr in a human clinical isolate of Enterococcus faecalis.
Nonmutational resistance to linezolid is due to the presence of cfr, which encodes a methyltransferase responsible for methylation of A2503 in the 23S rRNA. The cfr gene was first described in animal isolates of staphylococci, and more recently, it has been identified in Staphylococcus aureus from human clinical infections, including in an outbreak of methicillin-resistant S. aureus. In enterococci, cfr has been described in an animal isolate of Enterococcus faecalis from China. Here, we report an isolate of linezolid-resistant E. faecalis (603-50427X) recovered from a patient in Thailand who received prolonged therapy with the antibiotic for the treatment of atypical mycobacterial disease. The isolate lacked mutations in the genes coding for 23S rRNA and L3 and L4 ribosomal proteins and belonged to the multilocus sequence type (MLST) 16 (ST16), which is commonly found in enterococcal isolates from animal sources. Resistance to linezolid was associated with the presence of cfr on an ~97-kb transferable plasmid. The cfr gene environment exhibited DNA sequences similar to those of other cfr-carrying plasmids previously identified in staphylococci (nucleotide identity, 99 to 100%). The cfr-carrying plasmid was transferable by conjugation to a laboratory strain of E. faecalis (OG1RF) but not to Enterococcus faecium or S. aureus. The cfr gene was flanked by IS256-like sequences both upstream and downstream. This is the first characterization of the potential horizontal transferability of the cfr gene from a human linezolid-resistant isolate of E. faecalis.


The DUG Pathway Governs Degradation of Intracellular Glutathione in Aspergillus nidulans.
Glutathione (GSH) is an abundant tripeptide that plays a crucial role in shielding cellular macromolecules from various reactive oxygen and nitrogen species in fungi. Understanding GSH metabolism is of vital importance for deciphering redox regulation in these microorganisms. In the present study, to better understand the GSH metabolism in filamentous fungi, we investigated functions of the dugB and dugC genes in the model fungus Aspergillus nidulans These genes are orthologues of dug2 and dug3, which are involved in cytosolic GSH degradation in Saccharomyces cerevisiae The deletion of dugB, dugC, or both resulted in a moderate increase in the GSH content in mycelia grown on glucose, reduced conidium production, and disturbed sexual development. In agreement with these observations, transcriptome data showed that genes encoding mitogen-activated protein (MAP) kinase pathway elements (e.g., steC, sskB, hogA, and mkkA) or regulatory proteins of conidiogenesis and sexual differentiation (e.g., flbA, flbC, flbE, nosA, rosA, nsdC, and nsdD) were downregulated in the ΔdugB ΔdugC mutant. Deletion of dugB and/or dugC slowed the depletion of GSH pools during carbon starvation. It also reduced accumulation of reactive oxygen species and decreased autolytic cell wall degradation and enzyme secretion but increased sterigmatocystin formation. Transcriptome data demonstrated that enzyme secretions-in contrast to mycotoxin production-were controlled at the posttranscriptional level. We suggest that GSH connects starvation and redox regulation to each other: cells utilize GSH as a stored carbon source during starvation. The reduction of GSH content alters the redox state, activating regulatory pathways responsible for carbon starvation stress responses.IMPORTANCE Glutathione (GSH) is a widely distributed tripeptide in both eukaryotes and prokaryotes. Owing to its very low redox potential, antioxidative character, and high intracellular concentration, GSH profoundly shapes the redox status of cells. Our observations suggest that GSH metabolism and/or the redox status of cells plays a determinative role in several important aspects of fungal life, including oxidative stress defense, protein secretion, and secondary metabolite production (including mycotoxin formation), as well as sexual and asexual differentiations. We demonstrated that even a slightly elevated GSH level can substantially disturb the homeostasis of fungi. This information could be important for development of new GSH-producing strains or for any biotechnologically relevant processes where the GSH content, antioxidant capacity, or oxidative stress tolerance of a fungal strain is manipulated.


Taxonomy of two endemic Indian skinks, Eutropis bibronii (Gray, 1838)<br />and E. nagarjunensis (Sharma, 1969) (Reptilia: Scincidae), including redescriptions of their types.
Tiliqua bibronii was described by J.E. Gray in December, 1838 based on two syntypes (MNHN-RA 2940, 7076), but the details for locality was missing. These syntypes are currently housed at the Muséum national d'Histoire naturelle, Paris, France (MNHN-RA). The same species (based on the same type specimens) was described by A.M.C. Duméril & G. Bibron in November, 1839 nearly one year after Gray's publication. As such, Gray's publication must therefore be given priority. Another species, Euprepis trilineatus, from Madras, Tamil Nadu, India, was described by Gray in 1846, and it is morphologically similar to E. bibronii. Later, Boulenger (1885) synonymised it with E. bibronii. Eutropis bibronii has subsequently been recorded from other parts of India and Sri Lanka by various authors. Many years later, a closely related species, Mabuya nagarjuni (sic) Sharma, 1969, was described from Andhra Pradesh, India, based on two specimens (a holotype and a paratype) housed at the Zoological Survey of India, Kolkata (ZSI). Here we make a correction for the species epithet as "nagarjunensis" which should be a toponym, not a patronym. Among the skink collections at the Natural History Museum, London (BMNH), ZSI, and MNHN-RA we found E. bibronii specimens collected from various locations in India, but we were unable to find any specimens from Sri Lanka. Based on morphological evidence, E. bibronii represents a single, fairly widespread, species which has to be considered endemic to India. Although, recent phylogenetic studies reveal a distinct genetic divergence between E. bibronii and E. nagarjunensis, both species are morphologically very similar to each other. Here, we examine the morphology of E. nagarjunensis based on the ZSI specimens. A comprehensive comparison between the syntypes of E. bibronii and Euprepis trilineatus confirms that the latter nomen is a junior synonym of the former. The original description of E. bibronii is extremely concise and lacks most of the important diagnostic characters, so here we provide a comprehensive redescription of the species based on the examination of its syntypes.


Percutaneous endoscopic gastrostomy (PEG), in elderly patients with dementia and anorexia. Medical and ethical issues regarding placement.
Ethical and medico-legal issues reviews of Percutaneous Endoscopic Gastrostomy (PEG) placement in elderly patients is an important topic of international medical literature. PEG is often inappropriately placed in patients with not spontaneous oral feeding intake, cause of unrealistic expectations. We performed a critical review of the literature for placement of PEG in geriatric patients. A literature review was performed about the positioning of the PEG in geriatric patients with dementia and severe anorexia. This assessment has served to develop an algorithm that would be able to provide adequate indications for PEG placement in this patient population. We obtained appropriate indications about PEG placement, below: 1) Esophageal obstructions (like esophageal or neck cancer) 2) neurological deficits correlated dysphagia (like ictus sequelae) 3) refusal to swallow without concomitant terminal illness (like protracted pseudo dementia caused by severe depression) 4) chronic gastric decompression in patients with benign/malignant obstruction who do not wish or can't have a nasogastric tube placed. When compared with controls matched for age, elderly patients with cognitive impairment who have feeding gastrostomy do not demonstrate improved survival. Anorexia, Dementia, Elderly, Percutaneous Endoscopic Gastrostomy.


Nitrogen flux across ovine maternal and fetal hindquarters during fasting.
Nitrogen flux across the hindquarters of fetal and maternal sheep (n = 15) was determined during normal feeding and following 5 days of maternal fasting. Arterial and venous whole blood concentrations of free amino acids, ammonia and oxygen were measured entering and exiting the hindquarters. Further, the DNA, protein and nitrogen contents of the hindlimb skeletal muscle of the fetus were determined in the fed state and following the 5-day fast. Results of these studies indicate that maternal and fetal hindlimb metabolism differ during fasting. There is a net efflux of alanine, glutamine and total nitrogen from the maternal hindquarters following 5 days of fasting. The fetus also releases glutamine and alanine from the hindquarters during the fast, presumably as potential energy substrate. However, nitrogen balance across the fetal hindquarter remains positive as a result of increased positive arteriovenous differences for other amino acids (particularly leucine and isoleucine). The concentrations of DNA, protein and nitrogen in fetal skeletal muscle remain unchanged during fasting. These data indicate that, whereas the mother undergoes protein catabolism and net nitrogen loss from the hindquarter during fasting, the fetus maintains a positive nitrogen balance across the hindquarter.


Endocrine disruption and differential gene expression in sentinel fish on St. Lawrence Island, Alaska: Health implications for indigenous residents.
People living a subsistence lifestyle in the Arctic are highly exposed to persistent organic pollutants, including polychlorinated biphenyls (PCBs). Formerly Used Defense (FUD) sites are point sources of PCB pollution; the Arctic contains thousands of FUD sites, many co-located with indigenous villages. We investigated PCB profiles and biological effects in freshwater fish (Alaska blackfish [Dallia pectoralis] and ninespine stickleback [Pungitius pungitius]) living upstream and downstream of the Northeast Cape FUD site on St. Lawrence Island in the Bering Sea. Despite extensive site remediation, fish remained contaminated with PCBs. Vitellogenin concentrations in males indicated exposure to estrogenic contaminants, and some fish were hypothyroid. Downstream fish showed altered DNA methylation in gonads and altered gene expression related to DNA replication, response to DNA damage, and cell signaling. This study demonstrates that, even after site remediation, contaminants from Cold War FUD sites in remote regions of the Arctic remain a potential health threat to local residents - in this case, Yupik people who had no influence over site selection and use by the United States military.


Investigation on the Microporosity Formation of IN718 Alloy during Laser Cladding Based on Cellular Automaton.
Porosity is one of the most common defects in the laser cladding of Inconel 718 (IN718) alloy, which can reduce the strength and fatigue performance of the components. However, the dynamic formation of microporosity is challenging to observe through experiments directly. In order to explore the formation mechanism of porosities and dynamically reproduce the competitive growth between porosities and dendrite, a multi-scale numerical model was adopted, combined with a cellular automaton (CA) and finite element method (FEM). The decentered square algorithm was adopted to eliminate crystallographic anisotropy and simulate dendrite growth in different orientations. Afterward, based on the formation mechanism of microporosity during solidification, equiaxed and columnar dendrites with porosities were simulated, respectively. Dendrite morphology, porosity morphology, and distribution of solute concentration were obtained during the solidification process. The simulation results were reasonably compared with experimental data. The simulation results of the equiaxed crystal region are close to the experimental data, but the columnar crystal region has a relative error. Finally, the interaction effects of porosities and dendrites under different environmental conditions were discussed. The results suggested that with the increase in the cooling rate, the quantity of porosity nucleation increased and the porosity decreased.


Empowering nurses through inclusive leadership to promote research capacity building: A James Lind Alliance priority setting Partnership in Community Nursing.
This paper focuses on the benefits of inclusive leadership when undertaking a priority setting partnership in community nursing, through providing a collaborative and committed nurse-led forum for initiating impactful changes, identifying evidence uncertainties and driving research capacity-building initiatives. This is a Discussion paper. The project was undertaken between 2020 and 2021. This paper is based on shared reflections as 70@70 Senior Nurse Research Leaders and is supported by literature and theory. It draws on issues relating to collective leadership, stakeholder engagement, diversity, inclusivity and COVID-19. The James Lind Alliance Priority Setting Partnership catalysed the development of a rigorous evidence-base in community nursing. The collaborative opportunities, networks and connections developed with patients, carers, nursing leaders, policy makers and healthcare colleagues raised the profile of community nursing research. This will benefit nursing research, practice, education and patients in receipt of community nursing care. Collective buy in from national leaders in policy, education, funding and commissioning has secured a commitment that the evidence uncertainties will be funded. Four key learnings emerged: collective leadership can ensure learning is embedded and sustained; developing an engaged stakeholder community to promote community nursing research is essential; a diverse membership ensures inclusivity and representation; and insights into the impact of COVID-19 aid progress. The process increased research engagement and created capacity and capability-building initiatives. This will help community nurses feel empowered to lead changes to practice. Sustained engagement and commitment are required to integrate research priorities into community nursing research, education and practice and to drive forward changes to commissioning and service delivery. The study promoted research capacity building through inclusive leadership. This can increase community nurses' research engagement and career development and patient care quality and safety; this can incentivize funders and policy makers to prioritize community nursing research.


Ultrasound attenuation measurements using a reference phantom with sound speed mismatch.
Ultrasonic attenuation may be measured accurately with clinical systems and array transducers by using reference phantom methods (RPM) to account for diffraction and other system dependencies on echo signals. Assumptions with the RPM are that the speeds of sound in the sample (c(sam)) and in the reference medium (c(ref)) are the same and that they match the speed assumed in the system beamformer (c(bf)). This work assesses the accuracy of attenuation measurements by the RPM when these assumptions are not met. Attenuation was measured for two homogeneous phantoms, one with a speed of sound of 1500 m/s and the other with a sound speed of 1580 m/s. Both have an attenuation coefficient approximately equal to that of the reference, in which the speed of sound is 1540 m/s. Echo signals from the samples and the reference were acquired from a Siemens S2000 scanner with a 9L4 linear array transducer. Separate acquisitions were obtained with c(bf) at its default value of 1540 m/s and when it was set at values matching the speeds of sound of the phantoms. Simulations were also performed using conditions matching those of the experiment. RPM-measured attenuation coefficients exhibited spatially-dependent biases when c(sam) differed from c(df) and c(ref). Mean errors of 19% were seen for simulated data, with the maximum errors in attenuation measurements occurring for regions of interest near the transmit focus. Biases were minimized (mean error with simulated data was 5.6%) using c(bf) that matched c(sam) and assuring that power spectra used for attenuation computations in the sample are from precisely the same depth as those from the reference. Setting the transmit focus well beyond the depth range used to compute attenuation values minimized the bias.


Relationship of clinical features and laboratory parameters to thyroid echogenicity measured by standardized grey scale ultrasonography in patients with Hashimoto's thyroiditis.
Hashimoto's thyroiditis is associated with a diffuse reduction in thyroid echo levels. The purpose of this study was to determine the degree of hypoechogenicity in correlation to clinical features and laboratory parameters. 52 patients with Hashimoto's thyroiditis under substitutive therapy with levothyroxine (50-200 g daily) and 100 normal euthyroid volunteers (with no features of autoimmune disease who were not taking any thyroid medication) as controls were investigated. Determination of plasma free thyroxine (FT4) and TSH as well as peroxidase- (TPO), thyroglobulin- and TSH receptor (TSH-R) antibodies were performed. Thyroid volume was measured by conventional ultrasonography. Tissue echogenicity was characterized by standardized grey scale ultrasonography under defined operating conditions. Mean densities were given in a histogram range of grey scales between 0-63 GWE (= Grauwerteinheiten). Patients with Hashimoto's thyroiditis revealed significantly lower echo levels (19.6+/-2.6 GWE) than controls (25.6+/-2.0 GWE, p<0.001). High graded hypoechogenicity was associated with large goiters, persistently increased TSH levels (subclinical hypothyroidism) and highly elevated TPO-antibodies. Standardized grey scale ultrasonography allows for reproducable correlations between functional status and morphological characteristics of the thyroid gland in Hashimoto's thyroiditis. The results hint at a stronger inflammatory process in higher grades of hypoechogenicity.


Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer.
The analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans. The ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2. In this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560-0.788), ERG (AUC 0.785 (CI:0.680-0.890), PCA3 (AUC 0.681 (CI:0.567-0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600-0.888), and TMPRSS2 (AUC 0.637 (CI:0.519-0.754). This pilot study suggests that urinary EVs have the potential to be used as a platform to non-invasively differentiate patients with prostate cancer with very good accuracy. Larger studies are needed to confirm the potential for clinical utility.


Effect of matrix heterogeneity on cell mechanosensing.
Cells sense mechanical signals within the extracellular matrix, the most familiar being stiffness, but matrix stiffness cannot be simply described by a single value. Randomness in matrix structure causes stiffness at the scale of a cell to vary by more than an order of magnitude. Additionally, the extracellular matrix contains ducts, blood vessels, and, in cancer or fibrosis, regions with abnormally high stiffness. These different features could alter the stiffness sensed by a cell, but it is unclear whether the change in stiffness is large enough to overcome the noise caused by heterogeneity due to the random fibrous structure. Here we used a combination of experiments and modeling to determine the extent to which matrix heterogeneity disrupts the potential for cell sensing of a locally stiff feature in the matrix. Results showed that, at the scale of a single cell, spatial heterogeneity in local stiffness was larger than the increase in stiffness due to a stiff feature. The heterogeneity was reduced only for large length scales compared to the fiber length. Experiments verified this conclusion, showing spheroids of cells, which were large compared to the average fiber length, spreading preferentially toward stiff inclusions. Hence, the propagation of mechanical cues through the matrix depends on length scale, with single cells being able to sense only the stiffness of the nearby fibers and multicellular structures, such as tumors, also sensing the stiffness of distant matrix features.


Strut-autografting with and without osteogenic protein-1 : a preliminary study of a canine femoral head defect model.
Osteonecrosis of the femoral head frequently leads to collapse of the articular cartilage and to disabling osteoarthritis, which ultimately may necessitate joint arthroplasty. One treatment method that has had moderate success is the so-called trapdoor approach, which involves excavation of diseased (necrotic) bone followed by bone-grafting. Augmentation of this procedure with various growth and differentiation factors may improve the outcome. We developed a canine model that mimics the clinical situation with trapdoor bone-grafting. The objective of this study was to evaluate the effect of the addition of osteogenic protein-1 on healing following the trapdoor procedure with strut-autografting. Thirty-four skeletally mature dogs were used in the experiment. After capsulotomy, a trapdoor was created in the anterolateral surface of the femoral head and a 2-cm-diameter subchondral area of bone was removed. In the phase-I experiments, seven dogs had no treatment of the defect (Group I) and nine dogs were treated with strut-grafting (Group II). In phase II, the procedure was modified by collapsing the trapdoor into the created defect intraoperatively in eighteen dogs, which were divided into three equal groups: six untreated defects were left collapsed (Group III), six were treated with bone graft (Group IV), and six were treated with bone graft augmented with osteogenic protein-1 (Group V). Three of the seven femoral heads in Group I (untreated defect) and one of the nine heads in Group II (grafting without collapsing of the trapdoor) had evidence of cartilage collapse. Inspection of sagittal slices and radiographs revealed an unfilled residual defect in all Group-I heads, whereas all Group-II heads were well healed. The mean normalized stiffness value was significantly larger in Group II than it was in Group I. On visual inspection, depression was noted in all of the femoral heads in Group III (untreated defect; trapdoor left collapsed). In both Group IV and Group V (grafting without and with osteogenic protein-1), the trapdoor cartilage appeared to be essentially normal. Groups IV and V had more radiographic healing than did Group III. The defects in Group V (grafting with osteogenic protein-1) healed faster radiographically than did those in Group IV (grafting without osteogenic protein-1). Moderate-to-excellent healing was seen both radiographically and biomechanically by four months in the groups treated with grafting, with and without osteogenic protein-1, whereas untreated defects did not heal. Symptomatic osteonecrosis of the femoral head is a clinical challenge. The animal model in the current study is a useful tool for the evaluation of methods to treat osteonecrosis of the femoral head. Studies investigating additional time-periods between implantation of osteogenic protein-1 and assessment of results as well as different doses of osteogenic protein-1 are warranted.


CD48 is a low affinity ligand for human CD2.
COS cells transiently transfected with human CD48 were found to bind human PBL, whereas mock or CD7-transfected COS cells failed to bind human lymphocytes. Binding of PBL to CD48 transfectants was almost totally inhibited by either CD48 mAb pretreatment of COS cells or CD2 mAb pretreatment of PBL, implying an interaction between CD2 and CD48. This conclusion was confirmed by the demonstration that a highly fluorescent, multimeric form of rCD2 bound to CD48 transfected COS cells in a CD48-dependent manner. Additional mAb blocking studies revealed that CD48 interacts with the T11(1) region of CD2, the same region of CD2 that binds LFA-3 (CD58). Thus, CD48 and CD58 represent alternative and possibly competing ligands for CD2, although based on blocking studies with soluble CD2, CD48 interacts with CD2 with approximately a 100-fold lower affinity that CD58.


What is underneath all that stuff? A Q-methodological exploration of profiles of beliefs and vulnerabilities in hoarding disorder.
Hoarding disorder (HD) can be understood through the cognitive behavioural model in the context of vulnerability factors (for example, personality traits, co-morbidities, traumatic life events) and beliefs about possessions (for example, identity, emotional attachment, memory, utility). Less is known about the strength of these hypothesised beliefs, or how they interact within the hoarding population, with researchers suggesting that specifying beliefs would improve treatment outcomes. The current study explored beliefs in HD, utilising Q-methodology to explore both categories of beliefs and the interactions between these. Moreover, Q-methodology allowed for comparison of the individuals endorsing specific categories of beliefs. A comprehensive list of beliefs about possessions was developed. Thirty-two adults with clinically significant levels of HD completed a Q-sort task, alongside measures of proposed vulnerabilities, including co-morbidity, trauma and attachment style. Q-factor analysis produced four profiles consisting of groups of participants who endorsed the same beliefs and had shared characteristics: (1) 'Expression of identity', (2) 'Responsibility and morality', (3) 'Stability and predictability', and (4) 'Objects as emotional and meaningful beings'. The profiles were distinguished by different categories of beliefs and co-morbid symptoms, suggesting that more targeted assessment tools and interventions would be beneficial to account for this heterogeneity within the clinical population. In particular, beliefs about identity and self-concept formed the largest profile, and beliefs about stability and predictability introduce a novel category of beliefs.


Unequal Exposure or Unequal Vulnerability? Contributions of Neighborhood Conditions and Cardiovascular Risk Factors to Socioeconomic Inequality in Incident Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis.
Risk factors can drive socioeconomic inequalities in cardiovascular disease (CVD) through differential exposure and differential vulnerability. In this paper, we show how econometric decomposition directly enables simultaneous, policy-oriented assessment of these 2 mechanisms. We specifically estimate contributions of neighborhood environment and proximal risk factors to socioeconomic inequality in CVD incidence via these mechanisms. We followed 5,608 participants in the Multi-Ethnic Study of Atherosclerosis (2000-2012) to their first CVD event (median length of follow-up, 12.2 years). We used a summary measure of baseline socioeconomic position (SEP). Covariates included baseline demographics, neighborhood characteristics, and psychosocial, behavioral, and biomedical risk factors. Using Poisson models, we decomposed the difference (inequality) in incidence rates between low- and high-SEP groups into contributions of 1) differences in covariate means (differential exposure) and 2) differences in CVD risk associated with covariates (differential vulnerability). Notwithstanding large uncertainty in neighborhood estimates, our analysis suggested that differential exposure to poorer neighborhood socioeconomic conditions, adverse social environment, diabetes, and hypertension accounted for most of the inequality. Psychosocial and behavioral contributions were negligible. Further, neighborhood SEP, female sex, and white race were more strongly associated with CVD among low-SEP (vs. high-SEP) participants. These differentials in vulnerability also accounted for nontrivial portions of the inequality and could have important implications for intervention.


Incorporating sorption/desorption of organic pollutants into river water quality model.
Preliminary research was conducted about how to incorporate sorption/desorption of organic pollutants with suspended solids and sediments into single-chemical and one-dimensional water quality model of Jinghang Canal. Sedimentation-resuspension coefficient k3 was deduced; characteristics of organic pollutants, concentrations and components of suspended solids/sediments and hydrological and hydraulic conditions were integrated into k3 and further into river water quality model; impact of sorption/desorption of organic pollutants with suspended solids and sediments on prediction function of the model was discussed. Results demonstrated that this impact is pronounced for organic pollutants with relatively large Koc and Kow, especially when they are also conservative and f.o of river suspended solids/sediments is high, and that incorporation of sorption/desorption of organic pollutants into river water quality model can improve its prediction accuracy.


Motoneuron development influences dorsal root ganglia survival and Schwann cell development in a vertebrate model of spinal muscular atrophy.
Low levels of the survival motor neuron protein (SMN) cause the disease spinal muscular atrophy. A primary characteristic of this disease is motoneuron dysfunction and paralysis. Understanding why motoneurons are affected by low levels of SMN will lend insight into this disease and to motoneuron biology in general. Motoneurons in zebrafish smn mutants develop abnormally; however, it is unclear where Smn is needed for motoneuron development since it is a ubiquitously expressed protein. We have addressed this issue by expressing human SMN in motoneurons in zebrafish maternal-zygotic (mz) smn mutants. First, we demonstrate that SMN is present in axons, but only during the period of robust motor axon outgrowth. We also conclusively demonstrate that SMN acts cell autonomously in motoneurons for proper motoneuron development. This includes the formation of both axonal and dendritic branches. Analysis of the peripheral nervous system revealed that Schwann cells and dorsal root ganglia (DRG) neurons developed abnormally in mz-smn mutants. Schwann cells did not wrap axons tightly and had expanded nodes of Ranvier. The majority of DRG neurons had abnormally short peripheral axons and later many of them failed to divide and died. Expressing SMN just in motoneurons rescued both of these cell types showing that their failure to develop was secondary to the developmental defects in motoneurons. Driving SMN just in motoneurons did not increase survival of the animal, suggesting that SMN is needed for motoneuron development and motor circuitry, but that SMN in other cells types factors into survival.


Bacterial Succession during Vermicomposting of Silver Wattle (Acacia dealbata Link).
Vermicomposting is the process of organic waste degradation through interactions between earthworms and microbes. A variety of organic wastes can be vermicomposted, producing a nutrient-rich final product that can be used as a soil biofertilizer. Giving the prolific invasive nature of the Australian silver wattle Acacia dealbata Link in Europe, it is important to find alternatives for its sustainable use. However, optimization of vermicomposting needs further comprehension of the fundamental microbial processes. Here, we characterized bacterial succession during the vermicomposting of silver wattle during 56 days using the earthworm species Eisenia andrei. We observed significant differences in α- and β-diversity between fresh silver wattle (day 0) and days 14 and 28, while the bacterial community seemed more stable between days 28 and 56. Accordingly, during the first 28 days, a higher number of taxa experienced significant changes in relative abundance. A microbiome core composed of 10 amplicon sequence variants was identified during the vermicomposting of silver wattle (days 14 to 56). Finally, predicted functional profiles of genes involved in cellulose metabolism, nitrification, and salicylic acid also changed significantly during vermicomposting. This study, hence, provides detailed insights of the bacterial succession occurring during vermicomposting of the silver wattle and the characteristics of its final product as a sustainable plant biofertilizer.