Influence of maternal health literacy on child participation in social welfare programs: the Philadelphia experience.
We examined the influence of maternal health literacy on child participation in social welfare programs. In this cohort, 20% of the mothers had inadequate or marginal health literacy. Initially, more than 50% of the families participated in Temporary Assistance for Needy Families (TANF), the Food Stamp Program, and Special Supplemental Nutrition Program for Women, Infants, and Children, whereas fewer than 15% received child care subsidies or public housing. In multivariate regression, TANF participation was more than twice as common among children whose mothers had adequate health literacy compared with children whose mothers had inadequate health literacy.


Amino acid control of asparagine synthetase: relation to asparaginase resistance in human leukemia cells.
Complete amino acid deprivation in mammalian cells causes a significant enhancement in gene expression for a number of important cellular activities; among these is asparagine synthetase (AS). The data presented demonstrate that, in both nonleukemic (rat Fao hepatoma cells) and human leukemia cells (MOLT-4, NALL-1, and BALL-1), AS mRNA levels, protein content, and enzymatic activity are induced after incubation in an otherwise complete tissue culture medium that is deficient in a single amino acid or in medium that has been depleted of the amino acid asparagine by the addition of asparaginase. Complete amino acid deprivation results in a concerted increase in AS mRNA, protein, and enzymatic activity, which, in conjunction with previously published research, suggests that the mechanism of this cellular response involves transcriptional control of the AS gene. Asparaginase treatment is a standard component of acute lymphoblastic leukemia therapy for which the effectiveness is related to the inability of these cells to upregulate AS activity to a sufficient level. With regard to the asparaginase sensitivity of the three human leukemia cell lines, there was a trend toward an inverse relation to the degree of AS expression. Selection for asparaginase-resistant MOLT-4 sublines resulted in enhanced AS mRNA and protein content regardless of whether the cells had been selected by asparaginase treatment directly or asparagine was removed from the culture medium. Collectively, the data illustrate that further advances in asparaginase therapy will require additional knowledge of amino acid-dependent regulation of AS gene expression and, conversely, that asparaginase resistance represents a model system for investigating metabolite control in a clinically relevant setting.


Validity of establishing pediatric reference intervals based on hospital patient data: a comparison of the modified Hoffmann approach to CALIPER reference intervals obtained in healthy children.
To compare pediatric reference intervals calculated using hospital-based patient data with those calculated using samples collected from healthy children in the community as part of the CALIPER study. Hospital-based data for 13 analytes (calcium, phosphate, iron, ALP, cholesterol, triglycerides, creatinine, direct bilirubin, total bilirubin, ALT, AST, albumin and magnesium), measured on the Vitros 5600, collected between 2007 and 2011 were obtained. The data for each analyte were partitioned by age and gender as previously defined by the CALIPER study. Outliers in each partition were removed using the Tukey method. The cumulative distribution function (cdf) was then determined for each analyte value following which, the inverse cdf values of a standard Gaussian distribution were calculated. The analyte values were plotted against the inverse cdf of the standard Gaussian distribution. Piece-wise regression determined the linear portion of the resulting graph using the statistical software R. Linear regression determined an equation for the linear portion in each partition and reference intervals were calculated by extrapolating to identify the 2.5th and 97.5th centiles in each partition based on the inverse cdf values (which would correspond to the values -1.96 and 1.96 of the Gaussian distribution). Using the 90% confidence intervals for the reference intervals defined by CALIPER and the Reference Change Value (RCV) as the criteria, these calculated reference intervals were compared to those reported previously by CALIPER. Reference samples were also measured on the Vitros 5600 analyzer in an attempt to validate the calculated reference intervals. In general, the reference intervals calculated from hospital-based data were generally wider than those calculated by CALIPER. None of the reference intervals calculated using the Hoffmann approach fell completely within the 90% confidence intervals calculated by CALIPER. These results suggest that calculating pediatric reference intervals from hospital-based data may be useful, as a guide, in some cases but will likely not replace the need to establish reference intervals in healthy pediatric populations.


The role of intraoperative pulmonary arterial catheterization data in determining the need for extracorporeal membrane oxygenation in lung transplantation.
This study aims to investigate predictive factors of identification of the need of patients for extracorporeal membrane oxygenation support during lung transplantation. A total of 63 patients (49 males, 14 females, mean age: 44.9±14.4 years; range, 14 to 64 years) who underwent lung transplantation in our institution between December 2016 and December 2019 were retrospectively analyzed. Demographic characteristics and perioperative clinical data of patients were recorded. After induction and pulmonary artery catheterization, cardiac output, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, systemic vascular resistance, and right atrial pressure were measured using the thermodilution technique. Thirty-three of the patients received extracorporeal membrane oxygenation support during surgery. The right atrial pressure (p<0.001), pulmonary capillary wedge pressure (p<0.002), mean pulmonary artery pressure (p<0.001), and pulmonary vascular resistance (p<0.001) were statistically significantly higher in the patients who required extracorporeal membrane oxygenation support intraoperatively. The systemic vascular resistance (p<0.032) was statistically significantly lower in the patients who required extracorporeal membrane oxygenation support intraoperatively. A mean pulmonary artery pressure of >39 mmHg (p<0.02) and a right atrial pressure of >12 mmHg (p<0.047) were independent risk factors for ECMO support intraoperatively during lung transplantation. Predicting the need of intraoperative extracorporeal membrane oxygenation support is of utmost importance in timing the need for mechanical support, protecting the new graft from high mechanical ventilator pressures, and adequately maintaining hemodynamic stability.


Plasmonic sensor with high figure of merit based on differential polarization spectra of elliptical nanohole array.
Using the difference of the polarization transmission spectra of elliptical nanohole arrays (ENAs), the figure of merit (FOM) of the sensor performance of ENA can be significantly improved, and is inversely proportional to the measurement resolution. By optimizing the aspect ratio of the elliptical holes, Ag thickness, substrate-effect, and adhesive layer, the sensitivity, FOM, and relative sensitivity of the ENA can be improved to be 775 nm RIU-1, 705 RIU-1, and 70.23%, respectively, with an excellent linear dependence on the change of refractive index. Such a high-performance sensor also can be used in monitoring the molecule adsorption and RNA hybridization, revealing a highly localized near-field enhancement. This will benefit the sensing of surface-specific binding events in biologic detection and medical diagnosis.


Graduate foundation scheme with a focus on dignity and older adults.
The care experiences of older people in Wales and the rest of the UK have risen to the top of the political agenda recently, and it is the role of nurse managers to find ways to meet the dignity agenda. A review by the Older People's Commissioner for Wales (Marks 2011) recommends that 'better knowledge of the needs of older people with dementia is needed, together with improved communication, training, support and standards of care'. In an effort to meet this recommendation, one healthcare organisation, Cwm Taf Health Board, has developed a graduate foundation programme that focuses on the dignity of older patients in various hospital settings. This article describes the development and implementation of the programme.


Potential and advantages of immunochemical methods for analysis of foods.
The technique of immunochemical analysis, including the principles involved, is described and the various types of assay are discussed. Application of these methods to the analysis of foods for residues of pesticides, contaminants, drug residues, and natural constituents is reviewed. Compared with conventional methods, immunoassays offer similar detection limits and greatly simplified sample preparation procedures.


Laryngopharyngeal pH measurement.
Most emergency department (ED) intubations are to prevent gastric contents aspiration. The incidence of aspiration is unknown and intubation has complications. Balancing these risks requires an idea of the incidence of aspiration. This study assessed one technique for investigating the aspiration risk in ED patients. Cricoid pressure is used to reduce this risk and the technique may also examine this manoeuvre. Cohorts of unconscious adult ED and elective surgical patients were recruited. The posterior pharyngeal wall pH was measured immediately before and after intubation. Pharyngeal pH was used to indicate risk of aspiration, and pH change to assess the efficacy of cricoid pressure. Eight ED and 48 control patients were recruited. In the ED cohort, pH ranged from 6.0 to 8.0 before intubation and 4.7 to 8.0 after intubation: a mean decrease of 0.3 (95% CI 1.5 decrease to 0.9 increase). In the control cohort pH ranged from 5.8 to 8.0 before intubation and 6.0 to 8.0 after intubation: a mean increase of 0.4 (95% CI 0.1 to 0.6 increase). This is a simple, cheap, and repeatable technique for assessing aspiration risk in emergency intubations. A larger study is required to assess the efficacy of cricoid pressure.


History of neuropsychology through epilepsy eyes.
In the 19th century, Hughlings Jackson relied on clinical history, seizure semiology, and the neurologic examination as methods for seizure localization to inform the first epilepsy surgeries. In the 20th century, psychological and neuropsychological tests were first employed as both diagnostic and prognostic measures. The contemporary practice of epilepsy evaluation and management includes neuropsychology as a critical component of epilepsy care and research, and epilepsy and neuropsychology have enjoyed a very special and synergistic relationship. This paper reviews how epilepsy has shaped the practice of neuropsychology as a clinical service by asking critical questions that only neuropsychologists were in a position to answer, and how clinical care of epilepsy patients has been significantly improved based on neuropsychology's unique contributions.


Characterization of a 95,000 molecule on sheep leucocytes homologous to murine Pgp-1 and human CD44.
The phagocyte glycoprotein-1 (Pgp-1) antigen of mice is a 94,000 MW molecule with a wide tissue distribution, but no attributed function. We produced a monoclonal antibody (mAb) termed 25-32 which recognizes the Pgp-1 molecule of numerous mammalian species, including humans and sheep. Preclearing experiments with I42/5, a rat anti-mouse Pgp-1 mAb that cross-reacts with human Pgp-1, established the specificity of 25-32 for human and sheep Pgp-1. Moreover, an antibody recognizing human CD44, termed F10-44-2, also reacted with the same molecule as that recognized by 25-32 and I42/5, so establishing the co-identity of CD44 and Pgp-1. Within the sheep thymus, Pgp-1 was expressed most strongly by medullary thymocytes and stromal cells, and by small numbers of cells at the subcapsular cortex. Pgp-1 was expressed early in thymic ontogeny; all 35-40-day gestation fetal sheep thymocytes were intensely Pgp-1+, but by 80 days the number of reactive thymocytes had decreased to adult levels. The expression of Pgp-1 on lymphocytes was markedly increased after stimulation with mitogens, or with phorbol esters and ionomycin. The highly conserved nature of Pgp-1 through evolution, its expression on virtually all cell types within the body, and its increased expression on rapidly dividing cells indicate that this molecule mediates an important function, possibly serving as a hormone or metabolite receptor.


British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society.
Mortality due to cryptogenic fibrosing alveolitis (CFA) is increasing, particularly in the elderly. Optimum management remains uncertain and previous studies of the disease have largely been from specialist centres. A national study was carried out of the presentation and initial management of CFA in the UK. All respiratory physicians in England, Scotland and Wales were invited to enter patients with newly diagnosed CFA over a two year period. CFA was diagnosed on histological grounds or according to clinical criteria which included the absence of a defined connective tissue disorder or pneumoconiosis. Participating physicians (n = 150) completed a questionnaire at patient entry and at all subsequent follow up visits and death. A total of 588 patients (373 men, 63%) were studied of whom 441 (75%) were referrals from primary care. Their mean (SD) age was 67.4 (10.0) years and median duration of symptoms at presentation was 9.0 months. Clubbing was more common in men (203/373; 54%) than in women (86/ 215; 40%); 209 patients (36%) were graded as severely breathless at presentation. A history of dust exposure (organic or inorganic) was present in 274 patients (47%) of whom 87 had had some exposure to asbestos. Subjects exposed to dust were more likely to have smoked and had slightly higher mean lung volumes, but were otherwise indistinguishable from those not exposed in terms of clinical presentation, management, and outcome. Transbronchial biopsy specimens were taken in 164 patients (28%) and open lung biopsy specimens in 73 (12%), but 60% had no histological diagnostic procedure. Biopsy procedures were more likely to be performed in younger patients, those with better lung function, and those with a history of asbestos exposure. At presentation a decision not to initiate specific treatment was made in 284 cases (48%). The decision to initiate treatment was made predominantly on symptomatic grounds. Two years after the close of entry to the study 266 patients (45%) had died. CFA is predominantly a disease of elderly patients and has a poor prognosis. Physicians generally considered CFA to be a clinical diagnosis and did not initiate treatment in up to half of patients at presentation.


A rapid, extensive, and transient transcriptional response to estrogen signaling in breast cancer cells.
We report the immediate effects of estrogen signaling on the transcriptome of breast cancer cells using global run-on and sequencing (GRO-seq). The data were analyzed using a new bioinformatic approach that allowed us to identify transcripts directly from the GRO-seq data. We found that estrogen signaling directly regulates a strikingly large fraction of the transcriptome in a rapid, robust, and unexpectedly transient manner. In addition to protein-coding genes, estrogen regulates the distribution and activity of all three RNA polymerases and virtually every class of noncoding RNA that has been described to date. We also identified a large number of previously undetected estrogen-regulated intergenic transcripts, many of which are found proximal to estrogen receptor binding sites. Collectively, our results provide the most comprehensive measurement of the primary and immediate estrogen effects to date and a resource for understanding rapid signal-dependent transcription in other systems.


The lived experience of adolescent mother trauma survivors: A narrative approach.
The present study is a qualitative exploration of the link between earlier trauma and adolescent mother identity. We examined whether the mothers in our study formed an identification with other adolescent mothers, why or why not, and whether that identity (or lack thereof) was influenced by earlier traumatic experience. Fourteen residents of Delaware County, Pennsylvania, who became mothers between the ages of 14 and 19 (four White, seven African American, two Latina, and one Multiracial) participated in semi-structured interviews. Semi-structured, in-depth narrative interviews explored personal and community views on and experiences with adolescent pregnancy and parenthood. Results suggest that although exposure to traumatic events early in life can prompt more favorable evaluations of adolescent mothers before becoming a member of the ingroup for some, earlier trauma can prompt others to reject ingroup among adolescent mothers. Adolescent pregnancy and parenthood programs should utilize a trauma lens.


Characterization of patients referred for non-specific intellectual disability testing: the importance of autosomal genes for diagnosis.
Genetic testing for non-specific intellectual disability (ID) presents challenges in daily clinical practice. Historically, the focus of the genetic elucidation of non-specific ID has been on genes on the X chromosome, and recent research has brought attention to the growing contribution of autosomal genes. In addition, next-generation sequencing (NGS) has greatly improved the ability to simultaneously analyze multiple genetic loci, making large panel testing a practical approach to testing for non-specific ID. We performed NGS analysis of a total of 90 genes implicated in non-specific ID. The 90 genes included 56 X-linked genes and 34 autosomal genes. Pathogenic variants were identified in 11 of 52 (21%) patient samples. Nine of the eleven cases harbored mutations in autosomal genes including AP4B1, STXB1, SYNGAP1, TCF4 and UBE3A. Our mutation-positive cases provide further evidence supporting the prevalence of autosomal mutations in patients referred for non-specific ID testing and the utility of their inclusion in multi-gene panel analysis.


Zinc regulates a switch between primary and alternative S18 ribosomal proteins in Mycobacterium tuberculosis.
The Mycobacterium tuberculosis genome encodes five putative 'alternative' ribosomal proteins whose expression is repressed at high Zn(2+) concentration. Each alternative protein has a primary homologue that is predicted to bind Zn(2+). We hypothesized that zinc triggers a switch between these paired homologous proteins and therefore chose one of these pairs, S18-1/S18-2, to study mechanisms of the predicted competition for their incorporation into ribosomes. Our data show that Zn(2+)-depletion causes accumulation of both S18-2 mRNA and protein. In contrast, S18-1 mRNA levels are unchanged to slightly elevated under Zn(2+)-limited conditions. However, the amount of S18-1 protein is markedly decreased. We further demonstrate that both S18 proteins interact with ribosomal protein S6, a committed step in ribosome biogenesis. Zn(2+) is absolutely required for the S18-1/S6 interaction while it is dispensable for S18-2/S6 dimer formation. These data suggest a model in which S18-1 is the dominant ribosome constituent in high zinc conditions, e.g. inside of phagosomes, but that it can be replaced by S18-2 when zinc is deficient, e.g. in the extracellular milieu. Consequently, Zn(2+)-depletion may serve as a signal for building alternative ribosomes when M. tuberculosis is released from macrophages, to allow survival in the extracellular environment.


Simultaneous measurement of cortisol in serum and saliva after different forms of cortisol administration.
To prove the clinical usefulness of cortisol measurements in saliva for the exact assessment of a patient's corticoid status under therapeutic hormone substitution, we measured simultaneously total cortisol in serum and non-protein-bound cortisol in saliva after administration of different forms of hydrocortisone (cortisol) in eight cortisol-suppressed, healthy male volunteers. The intravenous and oral administration of 20 mg of cortisol exceeds the binding capacity of the corticosteroid-binding globulin (CBG), leading to an increase of the ratio between salivary and serum cortisol at the higher cortisol concentrations in blood. After rectal administration of 100 mg of cortisol acetate, the serum cortisol concentration does not exceed the binding capacity of CBG, so the ratio between salivary and serum cortisol remains nearly constant. However, this ratio was higher after rectal administration than after intravenous and oral administration, probably because of weaker binding of the acetate form of cortisol to CBG. Thus, the salivary measurement of the non-protein-bound (i.e., biologically active) cortisol offers a convenient way to monitor the effectiveness of various forms of systemic corticoid substitution.


Integrating numerical cognition research and mathematics education to strengthen the teaching and learning of early number.
Research into numerical cognition has contributed to a large body of knowledge on how children learn and perform mathematics. This knowledge has the potential to inform mathematics education. Unfortunately, numerical cognition research and mathematics education remain disconnected from one another, lacking the proper infrastructure to allow for productive and meaningful exchange between disciplines. The present study was designed to address this gap. This study reports on the design, implementation, and effects of a 16-week (25-hour) mathematics Professional Development (PD) model for Kindergarten to Grade 3 educators and their students. A central goal of the PD was to better integrate numerical cognition research and mathematics education. A total of 45 K-3 educators and 180 of their students participated. To test the reproducibility and replicability of the model, the study was carried out across two different sites, over a two-year period, and involved a combination of two different study designs: a quasi-experimental pre-post-research design and a within-group crossover intervention design. The results of the first implementation (Year 1), indicated that compared to a control group, both teachers and students benefited from the intervention. Teachers demonstrated gains on both a self-report measure and a test of numerical cognition knowledge, while students demonstrated gains in number line estimation, arithmetic, and numeration. In Year 2, teachers in the intervention group demonstrated greater improvements than the control group on the self-report measure, but not the test of numerical cognition knowledge. At the student level, there was some evidence of gains in numeration. The current PD model is a promising approach to better integrate research and practice. However, more research is needed to determine in which school contexts the model is most effective.


Phylogenetic diversity, host-specificity and community profiling of sponge-associated bacteria in the northern Gulf of Mexico.
Marine sponges can associate with abundant and diverse consortia of microbial symbionts. However, associated bacteria remain unexamined for the majority of host sponges and few studies use phylogenetic metrics to quantify symbiont community diversity. DNA fingerprinting techniques, such as terminal restriction fragment length polymorphisms (T-RFLP), might provide rapid profiling of these communities, but have not been explicitly compared to traditional methods. We investigated the bacterial communities associated with the marine sponges Hymeniacidon heliophila and Haliclona tubifera, a sympatric tunicate, Didemnum sp., and ambient seawater from the northern Gulf of Mexico by combining replicated clone libraries with T-RFLP analyses of 16S rRNA gene sequences. Clone libraries revealed that bacterial communities associated with the two sponges exhibited lower species richness and lower species diversity than seawater and tunicate assemblages, with differences in species composition among all four source groups. T-RFLP profiles clustered microbial communities by source; individual T-RFs were matched to the majority (80.6%) of clone library sequences, indicating that T-RFLP analysis can be used to rapidly profile these communities. Phylogenetic metrics of community diversity indicated that the two sponge-associated bacterial communities include dominant and host-specific bacterial lineages that are distinct from bacteria recovered from seawater, tunicates, and unrelated sponge hosts. In addition, a large proportion of the symbionts associated with H. heliophila were shared with distant, conspecific host populations in the southwestern Atlantic (Brazil). The low diversity and species-specific nature of bacterial communities associated with H. heliophila and H. tubifera represent a distinctly different pattern from other, reportedly universal, sponge-associated bacterial communities. Our replicated sampling strategy, which included samples that reflect the ambient environment, allowed us to differentiate resident symbionts from potentially transient or prey bacteria. Pairing replicated clone library construction with rapid community profiling via T-RFLP analyses will greatly facilitate future studies of sponge-microbe symbioses.


Quantitative Accuracy of Penalized-Likelihood Reconstruction for ROI Activity Estimation.
Estimation of the tracer uptake in a region of interest (ROI) is an important task in emission tomography. ROI quantification is essential for measuring clinical factors such as tumor activity, growth rate, and the efficacy of therapeutic interventions. Accuracy of ROI quantification is significantly affected by image reconstruction algorithms. In penalized maximum-likelihood (PML) algorithm, the regularization parameter controls the resolution and noise tradeoff and, hence, affects ROI quantification. To obtain the optimum performance of ROI quantification, it is desirable to use a moderate regularization parameter to effectively suppress noise without introducing excessive bias. However, due to the non-linear and spatial-variant nature of PML reconstruction, choosing a proper regularization parameter is not an easy task. Our previous theoretical study [1] has shown that the bias-variance characteristic for ROI quantification task depends on the size and activity distribution of the ROI. In this work, we design physical phantom experiments to validate these predictions in a realistic situation. We found that the phantom data results match well the theoretical predictions. The good agreement between the phantom results and theoretical predictions shows that the theoretical expressions can be used to predict the accuracy of ROI activity quantification.


Direct and inverse problems for light scattered by rough surfaces.
Calculations are performed to relate the stylus profile of a one-dimensionally rough surface to the angular distribution of the light scattered by such a surface. In the direct problem, the angular distribution of the scattered light calculated from the profile is shown to agree with the measured one. In the inverse problem, the rms roughness and the autocorrelation function are found by a least-squares fit to the measured angular distribution. For the smoother surfaces, the rms roughness is mostly determined by the ratio between the power of the specular beam and the total power of the scattered light; the computed values are proportional to those calculated directly from the stylus profiles. The values of the parameters obtained by the least-squares fit are affected by a variety of errors and agree only partially with those obtained from the stylus profile.


Premature cognitive decline in specific domains found in young veterans with mTBI coincide with elder normative scores and advanced-age subjects with early-stage Parkinson's disease.
Epidemiologists report a 56% increased risk of veterans with (+) mild traumatic brain injury (mTBI) developing Parkinson's disease (PD) within 12-years post-injury. The most relevant contributors to this high risk of PD in veterans (+) mTBI is unknown. As cognitive problems often precede PD diagnosis, identifying specific domains most involved with mTBI-related PD onset is critical. To discern which cognitive domains underlie the mTBI-PD risk relationship proposed in epidemiology studies. This exploratory match-controlled, cross-sectional study was conducted in a medical school laboratory from 2017-2020. Age- and IQ-matched veterans with (+) and without mTBI, non-veteran healthy controls, and IQ-matched non-demented early-stage PD were compared. Chronic neurological, unremitted/debilitating diseases, disorders, dementia, and substance use among others were excluded. Veterans were or were not exposed to non-penetrating combat-related mTBI occurring within the past 7-years. No other groups had recent military service or mTBI. Cognitive flexibility, attention, memory, visuospatial ability, and verbal fluency were examined with well-known standardized neuropsychological assessments. Out of 200 volunteers, 114 provided evaluable data. Groups significantly differed on cognitive tests [F (21,299) = 3.09, p<0.0001]. Post hoc tests showed veterans (+) mTBI performed significantly worse than matched-control groups on four out of eight cognitive tests (range: p = .009 to .049), and more often than not performed comparably to early-stage PD (range: p = .749 to .140). We found subtle, premature cognitive decline occurring in very specific cognitive domains in veterans (+) mTBI that would typically be overlooked in a clinic setting, This result potentially puts them at-risk for continual cognitive decline that may portend to the eventual onset of PD or some other neurodegenerative disease.


[Causes of death of alcoholics].
An analysis of the representative material revealed a high rate of mortality among alcoholics, which was much higher than the similar rate among sex- and age-matched control subjects. The leading causes of death were accidents, injuries, poisoning, cardiovascular diseases and neoplasms. Other causes of mortality include suicide, liver cirrhosis and lung tuberculosis.


A resurgence in field research is essential to better understand the diversity, ecology, and evolution of microbial eukaryotes.
The discovery and characterization of protist communities from diverse environments are crucial for understanding the overall evolutionary history of life on earth. However, major questions about the diversity, ecology, and evolutionary history of protists remain unanswered, notably because data obtained from natural protist communities, especially of heterotrophic species, remain limited. In this review, we discuss the challenges associated with "field protistology", defined here as the exploration, characterization, and interpretation of microbial eukaryotic diversity within the context of natural environments or field experiments, and provide suggestions to help fill this important gap in knowledge. We also argue that increased efforts in field studies that combine molecular and microscopical methods offer the most promising path toward (1) the discovery of new lineages that expand the tree of eukaryotes; (2) the recognition of novel evolutionary patterns and processes; (3) the untangling of ecological interactions and functions, and their roles in larger ecosystem processes; and (4) the evaluation of protist adaptations to a changing climate.


Evaluation of a Quality Improvement Intervention That Eliminated Routine Use of Opioids After Cesarean Delivery.
To evaluate the effects of eliminating the routine use of oral opioids for postcesarean delivery analgesia on postcesarean opioid consumption. At a tertiary care center, we implemented a quality improvement intervention among faculty practice patients undergoing cesarean delivery, which consisted of 1) eliminating routine ordering of oral opioids after cesarean delivery, 2) implementing guidelines for ordering a short course of opioids when deemed necessary, and 3) coupling opioid prescribing at discharge to patterns of opioid use in-hospital combined with shared decision-making. All patients, both before and after the intervention, were administered neuraxial opioids and scheduled acetaminophen and nonsteroidal antiinflammatory medications in the absence of contraindications. The primary outcome was the percentage of women who used any opioids postoperatively in-hospital. Secondary outcomes included the percentage of women discharged with a prescription for opioids, the quantity of opioids used in-hospital, pain scores, satisfaction, opioid-related side effects, and opioid prescriptions ordered in the 6 weeks after delivery. The effects of this intervention were assessed based on a chart review of patient data and a survey of patients in the 12 weeks before and 12 weeks after the intervention. We evaluated the records of 191 postcesarean delivery patients before and 181 after the intervention. Less than half of women used oral opioids in-hospital after the intervention, 82 (45%) compared with 130 (68%) before (P<.001). However, there was no change in pain scores or overall satisfaction with pain relief. Postintervention, only 40% of patients were discharged with prescriptions for opioids compared with 91% of patients before the intervention (P<.001). Eliminating routine ordering of oral opioids after cesarean delivery is associated with a significant decrease in opioid consumption while maintaining the same levels of pain control and patient satisfaction. Oral opioids are not needed by a large proportion of women after cesarean delivery.


Family support, perceived self-efficacy and self-care behaviour of Turkish patients with chronic obstructive pulmonary disease.
The purpose of this study was to describe family support, self-efficacy perception and self-care behaviour among patients with chronic obstructive pulmonary disease and to ascertain the relationship between these variables. It is important to work at improving confidence in the patients' ability to follow a self-care regimen by increasing self-efficacy. Family support also plays an important role in self-care activities. The study design is descriptive and correlational. Of 230 patients with chronic obstructive pulmonary disease who were recruited for the study, 200 agreed to participate. The patients were recruited by the first author from an outpatient clinic in the Department of Chest Disease of a university hospital and a pulmonary hospital in Erzurum, eastern Turkey. Data were collected by using a demographic data form, the Perceived Social Support from Family Scale, the Chronic Obstructive Pulmonary Disease Self-efficacy Scale and the Alberto Chronic Obstructive Pulmonary Disease Self-care Behaviour Inventory. Although most participants (91.5%) perceived that they had family support and more than three quarters (73.0%) of the participants engaged in an adequate amount of self-care behaviours, only twenty five participants' (12.5%) perceived self-efficacy as high. There were statistically significant positive relationships between family support and self-care behaviour (r=0.302; p=0.01) and between self-efficacy and self-care behaviour (r=0.186; p=0.01). There was also a statistically significant positive relationship between family support and self-efficacy (r=0.412; p=0.01). The results of the study demonstrated weak to moderate, but statistically significant, relationships between family support and self-care behaviours, self-efficacy and self-care behaviour and family support and self-efficacy in Turkish patients with chronic obstructive pulmonary disease. The assessment of the family support, self-efficacy and self-care behaviours of the patients with chronic obstructive pulmonary disease should be an essential part of nursing practice. The study also provides the foundation for the conduct of future studies of self-care training for managing patients with chronic obstructive pulmonary disease.


Selective cobalt nanoparticles for catalytic transfer hydrogenation of N-heteroarenes.
Nitrogen modified cobalt catalysts supported on carbon were prepared by pyrolysis of the mixture generated from cobalt(ii) acetate in aqueous solution of melamine or waste melamine resins, which are widely used as industrial polymers. The obtained nanostructured materials catalyze the transfer hydrogenation of N-heteroarenes with formic acid in the absence of base. The optimal Co/Melamine-2@C-700 catalyst exhibits high activity and selectivity for the dehydrogenation of formic acid into molecular hydrogen and carbon dioxide and allows for the reduction of diverse N-heteroarenes including substrates featuring sensitive functional groups.


Effectiveness of interventions for people living with dementia and their carers in Chinese communities: protocol for a systematic review and meta-analysis of randomised controlled trials.
As the largest and most rapidly ageing population, Chinese people are now the major driver of the continued growth in dementia prevalence globally. The need for evidence-based interventions in Chinese communities is urgent. Although a wide range of pharmacological and non-pharmacological interventions for dementia have been trialled in Chinese populations, the evidence has not been systematically synthesised. This systematic review and meta-analysis aims to map out the interventions for people living with dementia and their carers in Chinese communities worldwide and compare the effectiveness of these interventions. This protocol followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist. We will search Chinese (China National Knowledge Infrastructure, WanFang DATA) and English bibliographical databases (MEDLINE, EMBASE, PsycINFO, CINAHL Plus, Global Health, WHO Global Index Medicus, Virtual Health Library, Cochrane CENTRAL, Social Care Online, BASE, MODelling Outcome and cost impacts of interventions for DEMentia (MODEM) Toolkit, Cochrane Database of Systematic Reviews), complemented by hand searching of reference lists. We will include studies evaluating the effectiveness of interventions for dementia or mild cognitive impairment in Chinese populations, using a randomised controlled trial design, and published between January 2008 and June 2020. We will use a standardised form to extract data and Version 2 of the Cochrane risk-of-bias tool for randomised trials to assess the risk of bias of the included studies. Collected data will be fully interpreted with narrative synthesis and analysed using pairwise and network meta-analyses to pool intervention effects where sufficient information is available. We will perform subgroup analysis and meta-regression to explore potential reasons for heterogeneity. No formal ethics approval is required for this protocol. The findings will facilitate the development of studies on interventions for dementia and timely inform dementia policymaking and practice. Planned dissemination channels include peer-reviewed publications, conference presentations, public events and websites. CRD42019134135.


Developmental stages of occupational therapy and the feminist movement.
Developmental stages characterize the growth of both the feminist movement and the field of occupational therapy. The human development stages described by Erik Erikson are used to compare the growth stages of these two groups to the human sequence. It is hypothesized that both female-dominated groups began with an "infancy" period in the early 1900s characterized by the beginnings of identity and confidence in their respective groups. Both continued to develop through stages corresponding to the childhood stages characterized by Erikson and into the adolescent acting out stages as characterized by the demonstrations of the 1960s. Present and future trends are explored in relation to developmental stages, as well as to implications for the field of occupational therapy in education, theory, and practice.


Translational research insights from completed HIV vaccine efficacy trials.
The development of a safe and effective HIV vaccine remains a challenge. The modest efficacy seen in the RV144 vaccine trial represented an important milestone for the field. Results from all efficacy studies done to date have generated new information, which has advanced the HIV vaccine field in important ways. In this article, we review the translational research insights from the vaccine efficacy trials completed and fully analyzed to date. We also describe the recent advances in the search for broadly neutralizing antibodies and discuss potential approaches to circumvent the challenge posed by the enormous diversity of HIV-1. The experience from the past 5 years highlights the importance of conducting efficacy studies that continue to move us closer toward the goal of a safe, effective, durable, and universal HIV preventive vaccine.


Phase I/IB study of polyadenylic-polyuridylic acid in patients with advanced malignancies: clinical and biologic effects.
The synthetic polynucleotide polyadenylic-polyuridylic acid (polyA:polyU) has shown antitumor activity in murine studies and human breast cancer. PolyA:polyU was evaluated in 25 cancer patients receiving weekly intravenous doses between 3 and 600 mg/m2. PolyA:polyU was well tolerated up to 600 mg/m2, with no doselimiting toxicity (all < grade 3). Side effects included mild elevation in temperature, fatigue, and mild hyperglycemia. No changes outside of the normal range in hematocrit, WBC count, platelet count, total bilirubin, or alkaline phosphatase were observed. Of 25 patients, 18 completed at least one cycle of 6 weeks, and 5 completed two cycles (median 6 weeks). Four patients had stable disease over 11-13 weeks of treatment, and no clinical responses were observed. At 24 h after the first treatment, there were no significant increases in biologic response (beta 2-microglobulin and neopterin in serum, or 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells). A small increase in beta 2-microglobulin was observed 24 h after the week 3 treatment (1.1-fold, p < 0.01). By the third week of treatment, 2-5A synthetase levels decreased slightly (to 80% of baseline, p < 0.01). No changes in cytokines IL-6, IL-12, tumor necrosis factor (TNF), or IL-2 receptor in serum were detected after 24 h of treatment. Thus, at these doses, polyA:polyU had no marked modulation on biologic responses in vivo, although this preparation significantly induced 2-5A synthetase in peripheral blood mononuclear cells in vitro. PolyA:polyU was well tolerated. An MTD was not reached but was greater than 600 mg/m2 on this weekly schedule.


James Braid's psychophysiology: a turning point in the history of dynamic psychiatry.
James Braid is both a neglected and integral figure in the history of dynamic psychiatry. With the introduction of his neurophysiologic theory of hypnosis in the early 1840s he buried Mesmer's doctrine of animal magnetism and established hypnotic phenomena as data suitable for scientific inquiry. He subsequently elaborated a sophisticated psychophysiology with emphasis on the psychology of suggestion and the phenomenon of double consciousness. His espousal of hypnotism as a tool of scientific investigation and his innovative use of hypnosis to cure hysterical paralysis profoundly influenced the debates of the 1880s and 1890s concerning suggestive therapeutics and the nature of hypnosis.


Ethanol steam reforming on Ni/Al2O3 catalysts: effect of the addition of Zn and Pt.
Ni-based catalysts supported on Zn-modified alumina were investigated in the ethanol steam reforming reaction. A commercial γ-alumina was impregnated with different amounts of zinc nitrate (0, 2, 5, 10, 15, 20 wt.% on Zn basis), calcined, and then impregnated with nickel nitrate aqueous solutions. The samples were characterized by a number of techniques: N(2) adsorption at 77 K, X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray fluorescence (XRF), and temperature-programmed reduction (TPR). Their catalytic behavior in the ethanol steam reforming reaction was studied at 873 K, with a H(2)O/ethanol ratio of 5:1. Two effects of the presence of Zn were detected. On the one hand, zinc modifies the surface structure and the surface chemistry of the catalysts by formation of zinc aluminates, and on the other hand, zinc oxide can be reduced to metallic zinc under reaction conditions, thus modifying the catalytic properties of the active phase. The presence of Zn increases the ethanol conversion to gaseous compounds as compared with the catalyst supported on the Zn-free commercial alumina. The addition of a small amount of Pt (1 wt.%) causes a beneficial effect in the reaction. When Ni catalysts were used without a previous reduction treatment, ethylene was formed in high amounts; however, the Pt-Ni catalysts need no reduction pre-treatment to achieve high H(2) yields (close to 70%) and showed a high stability versus time on stream because of the control of the production of ethylene, a coke precursor.


The effect of vitamin D status on different neuromuscular blocker agents reverse time
This study is aimed to investigate the effects of vitamin D levels on sugammadex and neostigmine reversal times. Eighty patients between the ages of 18 and 65 years, with ASA I-III status who were undergoing surgery under general anesthesia were included in the study. A double blind fashion was used to randomly divide all the patients into two groups. At the end of the operation, sugammadex 2 mg/kg was administered to one group (Group sugammadex) and atropine and neostigmine was administered to the other group (Group neostigmine) intravenously. In the data analysis stage, the group was divided into two subgroups according to sugammadex and group neostigmine in itself, with vitamin D levels above and below 30 ng/mL. Statistical analysis was performed on these 4 groups (Group neostigmine and vitamin D < 30 ng/mL), (Group neostigmine and vitamin D ≥ 30 ng/mL), ( Group sugammadex and vitamin D < 30 ng/mL), (Group sugammadex and vitamin D ≥ 30 ng/mL). When two responses to train of four (TOF) stimulation were taken, the following times were recorded until extubation phase. The time until TOF value 50%, 70%, 90%, and extubation were recorded. There were statistically significant differences between Group sugammadex and vitamin D < 30 ng/mL and Group sugammadex and vitamin D ≥ 30 ng/mL (P = 0.007) for extubation times and 50% TOF reach times (P = 0.015). However, there was no difference observed between Group neostigmine and vitamin D < 30 ng/mL and Group neostigmine and vitamin D ≥ 30 ng/mL (P = 0.999). Vitamin D deficiency is important for anesthesiologists in terms of muscle strength and extubation time. Vitamin D deficiency seems to affect sugammadex reverse times but seems not to affect neostigmine reverse times. This conclusion needs further studies.


Cardiac [99mTc]Tc-hydroxydiphosphonate uptake on bone scintigraphy in patients with hereditary transthyretin amyloidosis: an early follow-up marker?
There is a need for early quantitative markers of potential treatment response in patients with hereditary transthyretin (ATTRv) amyloidosis to guide therapy. This study aims to evaluate changes in cardiac tracer uptake on bone scintigraphy in ATTRv amyloidosis patients on different treatments. In this retrospective cohort study, outcomes of 20 patients treated with the transthyretin (TTR) gene silencer patisiran were compared to 12 patients treated with a TTR-stabilizer. Changes in NYHA class, cardiac biomarkers in serum, wall thickness, and diastolic parameters on echocardiography and NYHA class during treatment were evaluated. Median heart/whole-body (H/WB) ratio on bone scintigraphy decreased from 4.84 [4.00 to 5.31] to 4.16 [3.66 to 4.81] (p < .001) in patients treated with patisiran for 29 [15-34] months. No changes in the other follow-up parameters were observed. In patients treated with a TTR-stabilizer for 24 [20 to 30] months, H/WB ratio increased from 4.46 [3.24 to 5.13] to 4.96 [ 3.39 to 5.80] (p = .010), and troponin T increased from 19.5 [9.3 to 34.0] ng/L to 20.0 [11.8 to 47.8] ng/L (p = .025). All other parameters did not change during treatment with a TTR-stabilizer. A change in cardiac tracer uptake on bone scintigraphy may be an early marker of treatment-specific response or disease progression in ATTRv amyloidosis patients.


Sarcoplasmic reticulum Ca2+ transport and gene expression in congestive heart failure are modified by imidapril treatment.
This study was designed to test the hypothesis that blockade of the renin-angiotensin system improves cardiac function in congestive heart failure by preventing changes in gene expression of sarcoplasmic reticulum (SR) proteins. We employed rats with myocardial infarction (MI) to examine effects of an angiotensin-converting enzyme inhibitor, imidapril, on SR Ca(2+) transport, protein content, and gene expression. Imidapril (1 mg.kg(-1).day(-1)) was given for 4 wk starting 3 wk after coronary artery occlusion. Infarcted rats exhibited a fourfold increase in left ventricular end-diastolic pressure, whereas rates of pressure development and decay were decreased by 60 and 55%, respectively. SR Ca(2+) uptake and Ca(2+) pump ATPase, as well as Ca(2+) release and ryanodine receptor binding activities, were depressed in the failing hearts; protein content and mRNA levels for Ca(2+) pump ATPase, phospholamban, and ryanodine receptor were also decreased by approximately 55-65%. Imidapril treatment of infarcted animals improved cardiac performance and attenuated alterations in SR Ca(2+) pump and Ca(2+) release activities. Changes in protein content and mRNA levels for SR Ca(2+) pump ATPase, phospholamban, and ryanodine receptor were also prevented by imidapril treatment. Beneficial effects of imidapril on cardiac function and SR Ca(2+) transport were not only seen at different intervals of MI but were also simulated by another angiotensin-converting enzyme inhibitor, enalapril, and an ANG II receptor antagonist, losartan. These results suggest that blockade of the renin-angiotensin system may increase the abundance of mRNA for SR proteins and, thus, may prevent the depression in SR Ca(2+) transport and improve cardiac function in congestive heart failure due to MI.


Long-term management of differentiated thyroid cancer.
The surveillance and long-term management of patients with differentiated thyroid cancer are highly dependent upon the individual patient's risk for recurrent disease. A 30-year-old woman who presents with a 1-cm intrathyroidal papillary cancer requires minimal surveillance following primary therapy: yearly examinations and thyroglobulin measurements on L-thyroxine suppressive therapy, periodic chest radiographs, and initially, periodic neck ultrasound examinations if the right equipment is available. These should be sufficient to identify the unexpected neck or distant recurrence. A 65-year-old man who presents with a 4-cm follicular cancer invading the thyroid capsule and intrathyroidal blood vessels needs more extensive surveillance. In addition to chest radiographs, neck ultrasound studies, and serum thyroglobulin measurements while the patient is off L-thyroxine therapy, total-body 131I scanning should be done 12 months after remnant ablation, and even if no uptake is demonstrated, 131I scanning should be repeated at 24 or 60 months. Any patient who presents with grossly invasive or metastatic disease should be treated aggressively. If feasible, aggressive surgical treatment of recurrent disease is optimal and may be curative. 131I scanning and treatment may be repeated at 6- to 12-month intervals for slow-growing functional metastases. Rapidly growing metastases should be treated by external beam radiotherapy, which can follow surgical debulking, or be combined with radioiodine or chemotherapy. Unfortunately, chemotherapy is of limited value in late metastatic disease, however, rarely it results in prolonged remission.


Connecticut State Special Olympics: observations and recommendations.
The Connecticut State Special Olympics provides an opportunity for thousands of developmentally challenged children and adults to participate in athletic events. This paper retrospectively reviews the demographics and documentation of medical problems in 1994, 1995, and 1996 Summer Games. The 1994 and 1995 summer games took place at the Coast Guard Academy and Connecticut College in New London. The 1996 summer games occurred at Fairfield and Sacred Heart Universities in Fairfield. The mean age of the participants ranged from 30 to 32 years of age. Minor trauma made up the largest percentage of encounters. Most of these injuries were sprains or strains to the lower extremities. The more serious injuries included dislocations and fractures. The incidence of seizure remained stable over these years. A comparison of the 1994, 1995, and 1996 games revealed a nearly 600 fold increase in heat-related dehydration in Fairfield as compared to the 1994 and 1995 games in New London. The highest incidence of sunburn occurred in 1995 despite the availability of sunblock. A concerted effort to reduce sunburn in the 1996 games in Fairfield resulted in a marked decrease of sunburn despite the higher temperatures, but an increase in chemical irritation to the eyes. Recommendations are presented to decrease the incidence of medical problems.


The Impact of Information Systems Use on Work Tasks and Work Practices in an Emergency Department.
This paper describes the plan for the third stage of a longitudinal assessment of the progressive implementation of IS in an emergency department. The assessment adopts a case study approach with nested mixed methods where quantitative data will be collected through observations and qualitative data will be collected through focus group interviews. The findings from the study can inform the design of IS that is well aligned with the intended strategic outcomes of IS implementation in emergency medicine.


Tobacco still a major killer-will we achieve the end game?
The game of tobacco use began in Europe in 1560 when the first tobacco seeds were sent from Lisbon to the king of France, by Jean Nicot. From kings' and nobles' exclusive use, it gradually and progressively became popular among the public, as a new player. Eighty-eight years ago (1929), Fritz Linkint, an extraordinary researcher in Germany, while reviewing existing evidence regarding a wide range of cancers potentially caused by smoking, indicated that smoking was a cause of respiratory disease. Despite the overwhelming accumulated evidence of the negative effects of nicotine intake, the prevalence of tobacco use is not expected to decline in the near future. What have we missed thus far in the game that claims more than seven million deaths annually worldwide? Although tobacco use is recognized as a major health problem, the persistent habit creates a dissonance between public health initiatives to reduce tobacco consumption and the choices citizens are making. To understand this dissonance, consideration first must be given to the social meaning attributed to smoking. Second, the political dissonance between health imperatives and social agendas is discussed with regard to relevant theory. Third, health promotion strategies can make a strong contribution to win the game from a negentropic perspective, that is to say, a public health vision that is structured towards an overarching goal.


A Robotized Soft Endoscope with Stereo Vision for Upper Gastrointestinal Endoscopic Submucosal Dissection (ESD).
This work presents a novel dual-segment flexible robotic endoscope designed to enhance reachability and dexterity during ESD surgery. The proposed system is capable of executing multi-angle cutting operations at a small angle relative to the lesion surface, allowing for efficient en-bloc resection. Additionally, the system incorporates two calibrated RGB cameras and a depth estimation algorithm to provide detailed 3D information of the tumour, which is used to guide the control framework. A stereo visual servoing controller is also implemented to improve path-following performance during surgery. Experiments results indicate that the proposed system improves motion stability and precision. The root means square error (RMSE) of circle path following is 1.1991mm with a maximum of 1.4751mm. Ex-vivo testing demonstrates its significant potential for use in endoscopic surgery.


Using an individualised consultation and activPAL™ feedback to reduce sedentary time in older Scottish adults: results of a feasibility and pilot study.
Sedentary behaviours have been linked to poor health, independent of physical activity levels. The objective of this study was to explore an individualised intervention strategy aimed at reducing sedentary behaviours in older Scottish adults. This feasibility and pilot study was a pre-experimental (one group pretest-posttest) study design. Participants were enrolled into the study in January-March 2012 and data analysis was completed April-October 2012. The study was based in Glasgow, Scotland. Participants received an individualised consultation targeting sedentary behaviour incorporating feedback from an activPAL activity monitor. Outcome measures were objectively (activPAL) and subjectively measured (Sedentary Behaviour Questionnaire) sedentary time. Twenty four participants received the intervention. Objectively measured total time spent sitting/lying was reduced by 24 min/day (p=0.042), a reduction of 2.2%. Total time spent in stepping activities, such as walking increased by 13 min/day (p=0.044). Self-report data suggested participants achieved behaviour change by reducing time spent watching television and/or using motorised transport. Interventions to reduce sedentary behaviours in older people are urgently needed. The results of this feasibility and pilot study suggest a consultation approach may help individuals reduce time spent in sedentary behaviours. A larger, controlled trial is warranted with a diverse sample to increase generalisability.


Diagnosing ICD-10 depressive episodes: superior criterion validity of the Patient Health Questionnaire.
Diagnosing and monitoring depression in primary care remains an issue of significant public health concern. Clinicians and researchers need to know if any one screening instrument is superior to the others in diagnosing ICD-10 depressive episodes. This study aimed to examine the criterion validity for diagnosing ICD-10 depressive episodes of the Patient Health Questionnaire (PHQ) in comparison with 2 well-established instruments, the Hospital Anxiety and Depression Scale (HADS), and the WHO Well-Being Index 5 (WBI-5). Five hundred and one medical outpatients completed the questionnaires and had a clinical interview. The presence of a depressive episode was determined with the International Diagnostic Checklists (IDCL) for ICD-10 as the criterion standard. Coefficient kappa (kappa), sensitivities and specificities were calculated and a statistical comparison of the areas under the receiver operating characteristic curves was performed. Diagnostic agreement between the questionnaires and the IDCL was moderate (kappa=0.34-0.56), with the highest values for the PHQ. While all 3 questionnaires had reasonable sensitivity and specificity, the operating characteristics for the PHQ were significantly superior to both the HADS and the WBI-5 (p=0.02). Any of the 3 screening instruments can be recommended for clinical use. However, this is the first comparative study to demonstrate the diagnostic advantage of a particular depression-screening instrument using the ICD-10 diagnostic criteria. The superior criterion validity of the PHQ is likely attributable to its closer representation of the current concept of depressive disorders.


BLINDNESS: ITS RELATION TO AGE OF MENARCHE.
Blindness in human females is associated with an age of menarche which is earlier than normal. When blindness is accompanied by a total loss of light perception, menarche is even earlier.


Novel components of the sex pheromones produced by emerald moths: identification, synthesis, and field evaluation.
The subfamily Geometrinae (Lepidoptera: Geometridae) includes many species called emerald moths. Based on our recent finding of novel polyenyl compounds, including a double bond at the 12-position from two geometrine species, Hemithea tritonaria and Thalassodes immissaria intaminata, (6Z,9Z,12Z)-6,9,12-trienes and (3Z,6Z,9Z,12Z)-3,6,9,12-tetraenes with a C(17)-C(20) straight chain were synthesized and analyzed by GC-MS. The 6,9,12-trienes, which were prepared by a double Wittig reaction between two alkanals and an ylide derived from (Z)-1,6-diiodo-3-hexene, characteristically produced fragment ions at m/z 79, 150, and M-98. The 3,6,9,12-tetraenes, which were prepared by a coupling between (Z)-3-alkenal and an ylide derived from (3Z,6Z)-1-iodo-3,6-nonadiene, showed fragment ions at m/z 79, 148, and M-96. These diagnostic ions were useful to distinguish these compounds from other known polyenyl pheromones, such as 4,6,9- and 6,9,11-trienes and 1,3,6,9-tetraenes. With reference to the GC-MS data, pheromone extracts of other species in Geometrinae inhabiting the Iriomote Islands were analyzed, and the 6,9,12-trienes were identified in the pheromone gland extracts of Pamphlebia rubrolimbraria rubrolimbraria and Maxates versicauda microptera. Furthermore, a field evaluation of the synthetic polyenes in a mixed forest of Tokyo revealed the following new male attractants for emerald moths: Idiochlora ussuriaria by a C(17) 6,9,12-triene and Jodis lactearia by a C(20) 3,6,9,12-tetraene, indicating the characteristic chemical structures of Geometrinae pheromones. On the other hand, through reexamination of the pheromone extract of H. tritonaria, (3E,6E)-α-farnesene was identified as an electrophysiologically active component in addition to the C(17) 6,9,12-triene. The binary mixture attracted more males than the single component lure baited with the triene in the Iriomote Islands.


Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial.
The IMMUNOBIL PRODIGE 57 trial is a non-comparative randomized phase II study assessing the efficacy and safety of the durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) combination with or without weekly paclitaxel in patients with advanced biliary tract carcinoma (BTC) after failure of platinum-based chemotherapy. Taxanes have already been safely combined with immune checkpoint inhibitors in other tumors. We report results of the 20-patient safety run-in. Patients received durvalumab (1500 mg at day 1 [D1] of each cycle)/tremelimumab (75 mg at D1 for 4 cycles; Arm A) or durvalumab/tremelimumab with paclitaxel (80 mg/m2 at D1, D8, D15; Arm B) every 28 days. Twenty patients were enrolled (Arm A/B: 10/10). There were no dose-limiting toxicities (DLTs) in Arm A. Six DLTs were observed in five patients (50%) in Arm B, meeting a stopping rule for the trial inclusions. DLTs included three serious anaphylactic reactions (with one cardiac arrest), two enterocolitis, and one infectious pneumopathy with septic shock. There were no patients with history of personal or familial auto-immune disease. The safety run-in part of IMMUNOBIL PRODIGE 57 raised concerns regarding co-administration of paclitaxel with durvalumab and tremelimumab in BTC, with an unexpected increase in anaphylactic adverse events. Phase II of the study will only evaluate the durvalumab and tremelimumab combination arm. NCT03704480.


The enzymes in ubiquitin-like post-translational modifications.
Ubiquitin and at least ten ubiquitin-like proteins are important post-translational modifiers that regulate nearly every aspect of cellular function. These modifications require several chemical reactions that are catalyzed by at least three enzymes. Significant progress has been made in the structure-function analysis of these enzymes. This review describes new advancements in an understanding of the mechanisms of the enzymes catalyzing ubiquitin-like modifications, and highlights the important problems that remain to be addressed.


Lack of a major role of Staphylococcus aureus Panton-Valentine leukocidin in lower respiratory tract infection in nonhuman primates.
Panton-Valentine leukocidin (PVL) is a two-component cytolytic toxin epidemiologically linked to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, including serious invasive infections caused by the epidemic clone referred to as strain USA300. Although PVL has long been known to be a S. aureus virulence molecule in vitro, the relative contribution of this leukotoxin to invasive CA-MRSA infections such as pneumonia remains controversial. We developed a nonhuman primate model of CA-MRSA pneumonia and used it to test the hypothesis that PVL contributes to lower respiratory tract infections caused by S. aureus strain USA300. The lower respiratory tract disease observed in this monkey model mimicked the clinical and pathological features of early mild to moderate S. aureus pneumonia in humans, including fine-structure histopathology. In this experiment using a large sample of monkeys and multiple time points of examination, no involvement of PVL in virulence could be detected. Compared with the wild-type parental USA300 strain, the isogenic PVL deletion-mutant strain caused equivalent lower respiratory tract pathology. We conclude that PVL does not contribute to lower respiratory tract infection in this nonhuman primate model of human CA-MRSA pneumonia.


Systematic Generation of the Dunham Coefficients Using Symbolic Mathematics Software.
The Dunham coefficients are an indispensable part of the analysis of the ro-vibrational spectrum of a diatomic molecule. They provide a direct connection between the ro-vibrational states observed and the interatomic potential that must exist in the molecule. One may deduce the interatomic potential from the spectrum or, alternatively, predict the spectrum from a theoretically generated interatomic potential. The coefficients result from a mathematical analysis of the Schrödinger equation for such a system. Dunham's derivation relied on the WKB approximation and, as such, was subject to the associated limitations. In this paper, the quantum condition is derived without any reliance on the WKB approximation, using only principles of complex analysis. This sidesteps the need for introducing an approximate function to join solutions and suggests that the expansion has a more fundamental basis. Also in this paper, a mathematical algorithm for generating the Dunham coefficients is elaborated in detail. Careful attention is paid to keeping these coefficients accurate to a specified order in the smallness parameter, τe = Be/ωe. This algorithm is intended to be presented in a way that makes it amenable to incorporation into computer code and points where the efficiency can be improved are indicated. Coefficients have been generated and presented in the literature through the years. The current paper presents the coefficients explicitly to tenth order in the smallness parameter, far more than have been generated in any previous work.


Automated detection and segmentation of intracranial hemorrhage suspect hyperdensities in non-contrast-enhanced CT scans of acute stroke patients.
Artif icial intelligence (AI)-based image analysis is increasingly applied in the acute stroke field. Its implementation for the detection and quantification of hemorrhage suspect hyperdensities in non-contrast-enhanced head CT (NCCT) scans may facilitate clinical decision-making and accelerate stroke management. NCCTs of 160 patients with suspected acute stroke were analyzed regarding the presence or absence of acute intracranial hemorrhages (ICH) using a novel AI-based algorithm. Read was performed by two blinded neuroradiology residents (R1 and R2). Ground truth was established by an expert neuroradiologist. Specificity, sensitivity, and area under the curve were calculated for ICH and intraparenchymal hemorrhage (IPH) detection. IPH-volumes were segmented and quantified automatically by the algorithm and semi-automatically. Intraclass correlation coefficient (ICC) and Dice coefficient (DC) were calculated. In total, 79 of 160 patients showed acute ICH, while 47 had IPH. Sensitivity and specificity for ICH detection were 0.91 and 0.89 for the algorithm; 0.99 and 0.98 for R1; and 1.00 and 0.98 for R2. Sensitivity and specificity for IPH detection were 0.98 and 0.89 for the algorithm; 0.83 and 0.99 for R1; and 0.91 and 0.99 for R2. Interreader reliability for ICH and IPH detection showed strong agreements for the algorithm (0.80 and 0.84), R1 (0.96 and 0.84), and R2 (0.98 and 0.92), respectively. ICC indicated an excellent (0.98) agreement between the algorithm and the reference standard of the IPH-volumes. The mean DC was 0.82. The AI-based algorithm reliably assessed the presence or absence of acute ICHs in this dataset and quantified IPH volumes precisely. • Artificial intelligence (AI) is able to detect hyperdense volumes on brain CTs reliably. • Sensitivity and specificity are highest for the detection of intraparenchymal hemorrhages. • Interreader reliability for hemorrhage detection shows strong agreement for AI and human readers.


Rapid differentiation of Staphylococcus aureus, Staphylococcus epidermidis and other coagulase-negative staphylococci and meticillin susceptibility testing directly from growth-positive blood cultures by multiplex real-time PCR.
This study evaluated a multiplex real-time PCR method specific for the mecA, femA-SA and femA-SE genes for rapid identification of Staphylococcus aureus, Staphylococcus epidermidis and non-S. epidermidis coagulase-negative staphylococci (CoNS), and meticillin susceptibility testing directly in positive blood cultures that grew Gram-positive cocci in clusters. A total of 100 positive blood cultures produced: 39 S. aureus [12 meticillin-resistant S. aureus (MRSA), 31% of all the S. aureus]; 30 S. epidermidis (56.6% of the CoNS), 8 Staphylococcus capitis (15.1%), 3 Staphylococcus saprophyticus (5.7%), 4 Staphylococcus hominis (7.5%), 3 Staphylococcus haemolyticus (5.7%), 2 Staphylococcus warneri (3.8%), 1 Staphylococcus cohnii (1.9%) and 2 unidentified Staphylococcus spp. (3.8%); and 1 Micrococcus luteus in pure culture. Two blood cultures had no growth on subculture and five blood cultures grew mixed CoNS. For the 95 blood cultures with pure growth or no growth on subculture, there was very good agreement between real-time PCR and the BD Phoenix identification system for staphylococcal species categorization in S. aureus, S. epidermidis and non-S. epidermidis CoNS and meticillin-resistance determination (Cohen's unweighted kappa coefficient κ=0.882). All MRSA and meticillin-susceptible S. aureus were correctly identified by mecA amplification. PCR amplification of mecA was more sensitive for direct detection of meticillin-resistant CoNS in positive blood cultures than testing with the BD Phoenix system. There were no major errors when identifying staphylococcal isolates and their meticillin susceptibility within 2.5 h. Further studies are needed to evaluate the clinical benefit of using such a rapid test on the consumption of glycopeptide antibiotics and the alteration of empiric therapy in the situation of positive blood cultures growing staphylococci, and the respective clinical outcomes.


NEEDS AND POSSIBILITIES OF SOCIAL WORK IN IMPLEMENTING SOCIAL INCLUSION WITH THE TOOLS OF ADAPTIVE PHYSICAL ACTIVITY.
Aim: reveal in social work the possibilities of applying adaptive physical activity in the process of social inclusion of persons with disabilities. Materials and Methods: To obtain factual information, the survey method (questionnaire) and a complex of mathematical statistics methods were used: methods of descriptive statistics and correlation analysis. Statistical analysis was performed using SPSS Statistics 24.0.0. A total of 102 anonymous respondents took part in the focus groups. Results: The connection between adaptive physical activity and the increase in the level of social inclusion of persons with disabilities, in particular, former military personnel and war veterans, was investigated. It was determined that social work professionals can use adaptive physical activity tools to promote the social inclusion of persons with disabilities and other low-mobility population groups. Conclusions: It was established that the ways of using adaptive physical activity tools by social workers for the social inclusion of persons with disabilities are most often socio-psychological, physical, professional rehabilitation, social support, and preventive activities. New opportunities for the implementation of social inclusion by means of adaptive physical activity of persons with disabilities as a result of military operations are opened in connection with the introduction of the position of «helper (assistant) of a veteran in the community», which will be held by a social worker.


Developing the Chemistry of Colloidal Cu Nanocrystals to Advance the CO₂ Electrochemical Reduction.
The ability to tailor make materials with atomic scale precision is crucial for understanding the sensitivities of their performance parameters and for achieving the design specification corresponding to optimal device operation. Herein, this topic is discussed in the context of catalysis. The electrochemical CO₂ reduction reaction (CO₂ RR) holds the promise to close the carbon cycle by storing renewable energies in chemical feedstocks, yet it suffers from the lack of efficient and selective catalysts. This article highlights how colloidal chemistry can contribute to tackle this compelling issue by designing shape-controlled nanocatalysts. In particular, two case studies relative to copper nanocrystals are discussed.


Vitamin C status, glutathione and histamine in gastric carcinoma, tuberculous enteritis and non-specific ulcerative colitis.
Studies were conducted to evaluate the blood levels of ascorbic acid, dehydroascorbic acid, glutathione, and histamine in patients with gastric carcinoma, tuberculous enteritis and non-specific ulcerative colitis. Leucocyte ascorbic acid, urinary excretion of total ascorbic acid and ascorbic acid saturation test were also carried out in order to assess the ascorbic acid status of these patients. It was observed that the plasma and leucocyte content of ascorbic acid was significantly lower with markedly decreased urinary excretion in these patients. Further urinary excretion of ascorbic acid after a test dose was also found to be subnormal. Decreased levels of glutathione and significantly higher levels of histamine reflect an overall reducing status of the body is markedly deranged.


Risk Assessment of Chlorogenic and Isochlorogenic Acids in Coffee By-Products.
Chlorogenic and isochlorogenic acids are naturally occurring antioxidant dietary polyphenolic compounds found in high concentrations in plants, fruits, vegetables, coffee, and coffee by-products. The objective of this review was to assess the potential health risks associated with the oral consumption of coffee by-products containing chlorogenic and isochlorogenic acids, considering both acute and chronic exposure. An electronic literature search was conducted, revealing that 5-caffeoylquinic acid (5-CQA) and 3,5-dicaffeoylquinic acid (3,5-DCQA) are the major chlorogenic acids found in coffee by-products. Toxicological, pharmacokinetic, and clinical data from animal and human studies were available for the assessment, which indicated no significant evidence of toxic or adverse effects following acute oral exposure. The current state of knowledge suggests that long-term exposure to chlorogenic and isochlorogenic acids by daily consumption does not appear to pose a risk to human health when observed at doses within the normal range of dietary exposure. As a result, the intake of CQAs from coffee by-products can be considered reasonably safe.


Regulon organization of Arabidopsis.
Despite the mounting research on Arabidopsis transcriptome and the powerful tools to explore biology of this model plant, the organization of expression of Arabidopsis genome is only partially understood. Here, we create a coexpression network from a 22,746 Affymetrix probes dataset derived from 963 microarray chips that query the transcriptome in response to a wide variety of environmentally, genetically, and developmentally induced perturbations. Markov chain graph clustering of the coexpression network delineates 998 regulons ranging from one to 1623 genes in size. To assess the significance of the clustering results, the statistical over-representation of GO terms is averaged over this set of regulons and compared to the analogous values for 100 randomly-generated sets of clusters. The set of regulons derived from the experimental data scores significantly better than any of the randomly-generated sets. Most regulons correspond to identifiable biological processes and include a combination of genes encoding related developmental, metabolic pathway, and regulatory functions. In addition, nearly 3000 genes of unknown molecular function or process are assigned to a regulon. Only five regulons contain plastomic genes; four of these are exclusively plastomic. In contrast, expression of the mitochondrial genome is highly integrated with that of nuclear genes; each of the seven regulons containing mitochondrial genes also incorporates nuclear genes. The network of regulons reveals a higher-level organization, with dense local neighborhoods articulated for photosynthetic function, genetic information processing, and stress response. This analysis creates a framework for generation of experimentally testable hypotheses, gives insight into the concerted functions of Arabidopsis at the transcript level, and provides a test bed for comparative systems analysis.


[Recurrent thrombophlebitis and bilateral gynecomastia. Primary manifestations of hepatocarcinoma].
Thirty-three-year-old male patient, without recognized risk factors, presenting with recurrent thrombophlebitis and bilateral gynecomastia as the only sign of feminization. Twenty-seven months after onset hepatocarcinoma of the right lobe was diagnosed. The rest of the liver was normal. Gynecomastia resolved after surgical removal of the tumor. Thromboembolism did not recur.


A mono-functional 3-deoxy-D-manno-octulosonic acid (Kdo) transferase and a Kdo kinase in extracts of Haemophilus influenzae.
Lipopolysaccharide of Haemophilus influenzae contains a single 3-deoxy-D-manno-octulosonic acid (Kdo) residue, linked to the 6' position of lipid A. In Escherichia coli and related organisms, a Kdo disaccharide is attached to lipid A. In previous studies, we cloned the gene (kdtA) encoding the E. coli Kdo transferase and demonstrated that homogeneous preparations of KdtA polypeptide catalyzed the attachment of both Kdo groups to the precursor, lipid IVA. E. coli KdtA produced only traces of mono-glycosylated product. We now show that a single Kdo is transferred to lipid IVA in extracts of H. influenzae. The mono-functional Kdo transferase of H. influenzae is membrane-bound, and the reaction is dependent upon a CMP-Kdo-generating system, as in E. coli. The specific activity of Kdo transfer to lipid IVA is 0.5-1 nmol/min/mg in H. influenzae membranes. Utilizing solubilized H. influenzae membranes, milligram quantities of Kdo-lipid IVA were prepared for analysis. Matrix-assisted laser desorption/ionization mass spectrometry revealed a parent ion (M - H)- at m/z 1626.0, consistent with the addition of a single Kdo moiety. Like lipid IVA, Kdo-lipid IVA was an excellent substrate for the bi-functional Kdo transferase of E. coli. In membranes of H. influenzae, but not E. coli, Kdo-lipid IVA was further phosphorylated in the presence of ATP, yielding a mono-phosphorylated Kdo-lipid IVA with a parent ion (M - H)- at m/z 1703.9. The identification of the mono-functional H. influenzae Kdo transferase, which is encoded by a KdtA homologue that displays 50% identity to its E. coli counterpart, should facilitate the mechanistic dissection of more complex multi-functional Kdo transferases, like those of E. coli and Chlamydia trachomatis.


Concurrent and Clonally Related Pediatric Follicular Lymphoma and Burkitt Lymphoma in a 5-Year-Old Boy.
Pediatric follicular lymphoma shares morphologic similarities with the adult form of the disease but lacks other classic features of adult lymphoma, including t(14;18) translocation, BCL2 overexpression, and transformation to aggressive higher-grade lymphoma. Herein, we report a novel case in which a 5-year-old boy (ethnicity unknown) had follicular lymphoma, along with concurrent high-grade and clonally related disease that fulfilled all of the morphologic, immunophenotypic, and genetic criteria for Burkitt lymphoma, including a t(8;14) translocation involving the MYC gene. To our knowledge, this case is the first reported instance of transformation of follicular lymphoma of any sort into true Burkitt lymphoma and the first reported instance of acquisition of MYC abnormalities in pediatric follicular lymphoma.


Tibial torsion among filipinos: a cadaveric study.
Tibial torsion, the twisting of the tibia about its long axis, can affect rotational positioning in total knee replacement. This angle varies depending on the ethnicity of the subject. There are no published studies to date to determine the tibial torsion among Filipinos. In this study, 28 cadaveric limbs were examined. Our results show that the average tibial torsion among adult Filipinos is 28.9°. Tibial torsion, Filipinos, cadaveric.


Change of mood during sleep and REM sleep variables.
Polysomnography was performed during two consecutive nights in 23 patients with major depression. After every final awakening patients estimated the change of their mood from evening to morning: 1. Mood worse in the morning than in the evening; 2. Mood does not change; 3. Mood better in the morning. When mood was estimated as being better in the morning (20% of all nights), eye movement density in REM sleep increased from the first to the fourth cycle. In all other nights eye movement density was slightly higher in the first than in subsequent cycles. Mood improvement correlated positively with eye movement density in the fourth cycle and negatively with REM sleep duration in the first cycle. Eye movement density in the first cycle correlated positively with the subjective estimation of sleep latency. A possible functional difference between initial and final REM sleep periods is proposed.


Curvature index of pincer nail.
Pincer nails are a common problem, and various treatments have been reported. However, there is no simple assessment of severity. We designed a curvature index for the nail plate to assess the severity of pincer nail. Measurement of the curvature index was as follows. The apparent width of the nail tip was defined as A, and the traced length of the nail tip was defined as B. The curvature index was defined as B divided by A (B/A). With this curvature index, it is easy to describe the severity of the pincer nail and to compare the improvement before and after treatment.


Photoluminescence characterization of KH₂PO₄ crystal: application to three-dimensional growth-sector identification.
In this work, rapidly grown KH2PO4 (KDP) crystals extracted from the prismatic and the pyramidal growth sectors of crystal boules were analyzed using photoluminescence measurements. From the spectra, we deduced a robust criterion to discriminate between both growth sectors in an unknown KDP plate. Moreover, spatially resolved photoluminescence was shown to enable a local probing of different planes in the bulk of the material leading to accurate and nondestructive three-dimensional mapping of the sector boundary, which is often the weakest point in terms of laser-damage resistance in rapidly grown KDP crystals.


Exogenous application of β-sitosterol mediated growth and yield improvement in water-stressed wheat (Triticum aestivum) involves up-regulated antioxidant system.
Water stress reduces crop production significantly, and climate change has further aggravated the problem mainly in arid and semi-arid regions. This was the first study on the possible effects of β-sitosterol application in ameliorating the deleterious changes in wheat induced by water stress under field condition and drip irrigation regimes. A field experiment with the split-plot design was conducted, and wheat plants were foliar sprayed with four β-sitosterol (BBS) concentrations (0, 25, 75, and 100 mg L-1) and two irrigation regimes [50 and 100% of crop evapotranspiration (ETc)]. Water stress without BBS treatment reduced biological yield, grain yield, harvest index, and photosynthetic efficiency significantly by 28.9%, 42.8%, 19.6%, and 20.5% compared with the well-watered plants, respectively. Proline content increased in water-stressed and BSS-treated plants, owing to a significant role in cellular osmotic adjustment. Application of BSS was effective in reducing the generation of hydrogen peroxide (H2O2) and hence the malondialdehyde content significantly in water-stressed and well-watered wheat plants. Application of BSS up-regulated the activity of antioxidant enzymes (SOD, CAT, POD, and APX) significantly and increased the content of tocopherol, ascorbic acid, and carotene thereby reducing the levels of reactive oxygen species. The increased antioxidant system in BSS treated plants was further supported by the expression level of SOD and dehydrin genes in both water-stressed and well-watered plants. In the present study, the application of BBS at 100 mg L-1 was beneficial and can be recommended for improving the growth and yield of the wheat crop under water stress.


Cerebral blood flow regulates iron overload in the cerebral nuclei of hemodialysis patients with anemia.
Hemodialysis patients exhibit anemia-related cerebral hyperperfusion and iron deposition (ID). However, the mechanisms underlying the pathology of cerebral ID are not clear. We investigated the role of cerebral blood flow (CBF) in the pathophysiology of cerebral ID in hemodialysis patients with anemia. This study recruited 33 hemodialysis patients with anemia and thirty-three healthy controls (HCs). All the subjects underwent quantitative susceptibility mapping (QSM) and arterial spin labeling (ASL) to measure ID and CBF in the cerebral nuclei. Furthermore, we evaluated lacunar infarction (LI), cerebral microbleeds, and total white matter hyperintensity volume (TWMHV). Hemodialysis patients with anemia showed significantly higher ID and CBF in some nuclei compared to the HCs after adjusting for age, sex, and total intracranial volume (TIV) [P < 0.05, false discovery rate (FDR) corrected]. CBF showed a positive correlation with ID in both patients and HCs after adjustments for age, gender, and TIV (P < 0.05, FDR corrected). Serum phosphorus, calcium, TWMHV, hypertension, and dialysis duration were independently associated with ID (P < 0.05). Hemoglobin, serum phosphorus, and LI were independently associated with CBF (P < 0.05). Mediation analysis demonstrated that CBF mediated the effects between hemoglobin and ID. Our study demonstrated that CBF mediated aberrant cerebral ID in hemodialysis patients with anemia.


Seroprevalence of Toxoplasma gondii antibodies in humans from rural Western Amazon, Brazil.
Antibodies to Toxoplasma gondii were assayed in sera of 266 humans from 71 farms located at Rondônia State, Western Amazon, Brazil, by the modified agglutination test (MAT) and the indirect immunofluorescent antibody test (IFAT). Antibodies were found in 195 humans (73.3%), with MAT titers of 1:25 in 11, 1:50 in 11, 1:100 in 16, 1:200 in 27, 1:400 in 38, 1:800 in 37, 1:1,600 in 22, and 1:3,200 or higher in 33. From the 71 farms visited, 69 had seropositive humans. Prevalence of anti-T. gondii antibodies increased with age of the people (P < 0.05), and no difference was observed in the occurrence by gender (P > 0.05). A sanitary questionnaire was applied in each farm, and statistical association between the serologic status and several variables were analyzed. Home-grown vegetable consumption and origin of drinking water (well or river) were the independent variables that displayed significant association (P = 0.002 and 0.02, respectively). Higher values of occurrence were found in people with consumption of home-grown vegetables (76.1%) and people that drink well water (75.4%) compared with people that did not consume this type of food (61.9%) and drink river water (55.2%). By IFAT (> or = 1:16), 194 of 266 (73%) humans were seropositive and there was a good correlation between MAT and IFAT.


Mutations at the Alphavirus E1'-E2 Interdimer Interface Have Host-Specific Phenotypes.
Alphaviruses are enveloped viruses transmitted by arthropod vectors to vertebrate hosts. The surface of the virion contains 80 glycoprotein spikes embedded in the membrane, and these spikes mediate attachment to the host cell and initiate viral fusion. Each spike consists of a trimer of E2-E1 heterodimers. These heterodimers interact at the following two interfaces: (i) the intradimer interactions between E2 and E1 of the same heterodimer and (ii) the interdimer interactions between E2 of one heterodimer and E1 of the adjacent heterodimer (E1'). We hypothesized that the interdimer interactions are essential for trimerization of the E2-E1 heterodimers into a functional spike. In this work, we made a mutant virus (chikungunya piggyback [CPB]) where we replaced six interdimeric residues in the E2 protein of Sindbis virus (wild-type [WT] SINV) with those from the E2 protein from chikungunya virus and studied its effect in both mammalian and mosquito cell lines. CPB produced fewer infectious particles in mammalian cells than in mosquito cells, relative to WT SINV. When CPB virus was purified from mammalian cells, particles showed reduced amounts of glycoproteins relative to the capsid protein and contained defects in particle morphology compared with virus derived from mosquito cells. Using cryo-electron microscopy (cryo-EM), we determined that the spikes of CPB had a different conformation than WT SINV. Last, we identified two revertants, E2-H333N and E1-S247L, that restored particle growth and assembly to different degrees. We conclude the interdimer interface is critical for spike trimerization and is a novel target for potential antiviral drug design. IMPORTANCE Alphaviruses, which can cause disease when spread to humans by mosquitoes, have been classified as emerging pathogens, with infections occurring worldwide. The spikes on the surface of the alphavirus particle are absolutely required for the virus to enter a new host cell and initiate an infection. Using a structure-guided approach, we made a mutant virus that alters spike assembly in mammalian cells but not mosquito cells. This finding is important because it identifies a region in the spike that could be a target for antiviral drug design.


Aberrantly Over-Expressed TRPM8 Channels in Pancreatic Adenocarcinoma: Correlation with Tumor Size/Stage and Requirement for Cancer Cells Invasion.
The transient receptor potential melastatin-subfamily member 8 (TRPM8) channels control Ca2+ homeostasis. Recent studies indicate that TRPM8 channels are aberrantly expressed and required for cellular proliferation in pancreatic adenocarcinoma. However, the functional significance of TRPM8 in pancreatic tissues is mostly unknown. The objectives of this study are to examine the expression of TRPM8 in various histopathological types of pancreatic tissues, determine its clinical significance in pancreatic adenocarcinoma, and investigate its functional role in cancer cells invasion. We present evidence that, in normal pancreatic tissues, anti-TRPM8 immunoreactivity is detected in the centroacinar cells and the islet endocrine cells. In pre-malignant pancreatic tissues and malignant neoplasms, TRPM8 is aberrantly expressed to variable extents. In the majority of pancreatic adenocarcinoma, TRPM8 is expressed at moderate or high levels, and anti-TRPM8 immunoreactivity positively correlates with the primary tumor size and stage. In the pancreatic adenocarcinoma cell lines that express relatively high levels of TRPM8, short hairpin RNA-mediated interference of TRPM8 expression impaired their ability of invasion. These data suggest that aberrantly expressed TRPM8 channels play contributory roles in pancreatic tumor growth and metastasis, and support exploration of TRPM8 as a biomarker and target of pancreatic adenocarcinoma.


Macro- and Microvascular Parameters After Toxic Shock Syndrome.
Whether individuals who had toxic shock syndrome in childhood have differences in macro- and retinal microvascular parameters indicative of increased cardiovascular risk is unknown. We found no evidence of adverse macrovascular changes in 22 toxic shock syndrome participants compared with 60 control participants. Microvascular comparisons showed a reduction in retinal total fractal dimension, which has been associated with cardiovascular risk factors in children.


PEGylated carbon nanotubes impair retrieval of contextual fear memory and alter oxidative stress parameters in the rat hippocampus.
Carbon nanotubes (CNT) are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate the neurotoxicity of these nanomaterials. The present work assessed the effects of single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG) on the consolidation and retrieval of contextual fear memory in rats and on oxidative stress parameters in the hippocampus. SWCNT-PEG were dispersed in water at concentrations of 0.5, 1.0, and 2.1 mg/mL and infused into the rat hippocampus. The infusion was completed immediately after training and 30 min before testing of a contextual fear conditioning task, resulting in exposure times of 24 h and 30 min, respectively. The results showed that a short exposure to SWCNT-PEG impaired fear memory retrieval and caused lipid peroxidation in the hippocampus. This response was transient and overcome by the mobilization of antioxidant defenses at 24 h. These effects occurred at low and intermediate but not high concentration of SWCNT-PEG, suggesting that the observed biological response may be related to the concentration-dependent increase in particle size in SWCNT-PEG dispersions.


Opportunistic mothers: female marmosets (Callithrix kuhlii) reduce their investment in offspring when they have to, and when they can.
All female primates incur energetic costs associated with producing and caring for offspring, but females belonging to the New World primate family Callitrichidae, the marmosets and tamarins, appear to face even further demands. In fact, the energetic demands of rearing callitrichid infants are thought to have led to the evolution of cooperative infant care in these species. If this explanation is true, then one might expect that natural selection should also have shaped patterns of maternal behavior to be sensitive to the costs of reproduction and equipped females to reduce their investment in offspring under certain conditions. Therefore, we examined the maternal effort and postpartum endocrine profiles of individual female marmosets (Callithrix kuhlii) across conditions that represented two hallmarks of callitrichid reproduction-conception during the early postpartum period and alloparental assistance. When females conceived during the early postpartum period and faced the upcoming demands of caring for their newly conceived litters (Study 1), they significantly reduced their caregiving effort and had significantly higher postpartum levels of estradiol relative to breeding attempts in which conception occurred later in the postpartum period. Postpartum estradiol was negatively correlated with maternal carrying effort. When experienced alloparents were present (Study 2), females again reduced their caregiving effort relative to breeding attempts in which experienced alloparents were not present. Postpartum cortisol, however, did not vary as a function of experienced alloparental assistance. The results of these studies suggest that female marmosets have been subjected to similar selection pressures as females of other primate taxa--to maximize their reproductive success by reducing their investment in offspring under the worst and best of conditions--and suggest that hormones may mediate within-female variation in maternal care. These studies also provide support for the notion that mothers are "flexible opportunists" when it comes to providing care to their young.


Differential innate immune responses to low or high dose oral SIV challenge in Rhesus macaques.
Mucosal transmission of HIV predominately occurs during sexual intercourse or breast-feeding and generally results in a successful infection from just one or few founder virions. Here we assessed the impact of viral inoculum size on both viral and immune events within two groups of Rhesus macaques that were non-traumatically, orally inoculated with either multiple low (1000 to 4000 TCID(50)) or high (100,000 TCID(50)) doses of SIV. In agreement with previous studies, more diverse SIV variants were observed in macaques following infection with high dose oral SIV compared to a low dose challenge. In peripheral blood cells, the immune gene transcript levels of CXCL9, IFNγ, TNFα and IL10 remained similar to uninfected macaques. In contrast, OAS and CXCL10 were upregulated following SIV infection in both the high and low dosed macaques, with a more rapid kinetics (detectable by 7 days) following the high SIV dose challenge. In peripheral lymph nodes, an increase in CXCL10 was observed irrespective of viral dose while CXCL9 and OAS were differentially regulated in the two SIV dosed groups. Magnetic bead sorting of CD3+, CD14+ and CD3- /CD14- cells from peripheral blood identified the increase in OAS expression primarily within CD14+ monocytes, whereas the CXCL10 expression was primarily in CD3+ T cells. These findings provide insights into the impact of SIV challenge dose on viral and innate immune factors, which has the potential to inform future SIV/HIV vaccine efficacy trials in which vaccinated hosts have the potential to be infected with a range of viral challenge doses.