Congruence and discrepancy between working alliance and real relationship: Variance decomposition and response surface analyses.
We examined how congruence and discrepancy in clients' and therapists' ratings of the working alliance (WA) and real relationship (RR) were related to client-rated session quality (SES; Session Evaluation Scale). Ratings for 2517 sessions of 144 clients and 23 therapists were partitioned into therapist-level, client-level, and session-level components and then analyzed using multilevel, polynomial regression and response surface analysis. For both clients and therapists, at all levels of analysis (except the therapist level for therapist ratings), SES was highest when combined WA and RR ratings were high, and lowest when combined ratings were low. For client ratings, discrepancy between WA and RR, at the client and session levels, was associated with greater session quality. Some clients perceived greater session quality when, across all sessions, WA was stronger than RR and other clients perceived greater session quality when RR was stronger than WA. Within clients, session quality was highest when some sessions had a stronger WA than RR whereas other sessions had a stronger RR than WA. These findings are compatible with a responsiveness framework, therapists varied the balance of WA and RR to suit situational demands or needs of different clients. When therapists rated WA and RR the opposite pattern of results emerged; clients perceived greater session quality when therapists' WA and RR ratings, for a session were high and consistent (i.e., no discrepancy between WA and RR). In addition, across all sessions, clients perceived greater session quality when WA and RR ratings were high and consistent. (PsycINFO Database Record


Squalene and cholesterol in dust from danish homes and daycare centers.
Given the rate at which humans shed their skin (desquamation), skin flakes that contain squalene and cholesterol are anticipated to be major constituents of indoor dust. These compounds have been detected in more than 97% of the dust samples collected from 500 bedrooms and 151 daycare centers of young children living in Odense, Denmark. The mass fractions of squalene in dust were approximately log-normally distributed (homes: GM = 32 μg/g, GSD = 4.3; daycare centers: GM = 11.5 μg/g, GSD = 4.3); those of cholesterol displayed a poorer fit to such a distribution (homes: GM = 625 μg/g, GSD = 3.4; daycare centers: GM = 220 μg/g, GSD = 4.0). Correlations between squalene and cholesterol were weak (r = 0.22). Furthermore, the median squalene-to-cholesterol ratio in dust (~0.05) was more than an order of magnitude smaller than that in skin oil. This implies sources in addition to desquamation (e.g., cholesterol from cooking) coupled, perhaps, with a shorter indoor lifetime for squalene. Estimated values of squalene's vapor pressure, while uncertain, suggest meaningful redistribution from dust to other indoor compartments. We estimate that dust containing squalene at 60 μg/g would contribute about 4% to overall ozone removal by indoor surfaces. This is roughly comparable to the fraction of ozone removal that can be ascribed to reactions with indoor terpenes. Squalene containing dust is anticipated to contribute to the scavenging of ozone in all settings occupied by humans.


Mitochondrial Genome Evolution and a Novel RNA Editing System in Deep-Branching Heteroloboseids.
Discoba (Excavata) is an evolutionarily important group of eukaryotes that includes Jakobida, with the most bacterial-like mitochondrial genomes known, and Euglenozoa, many of which have extensively fragmented mitochondrial genomes. However, little is known about the mitochondrial genomes of Heterolobosea, the third main group of Discoba. Here, we studied two heteroloboseids-an undescribed amoeba "BB2" and Pharyngomonas kirbyi. Phylogenomic analysis revealed that they form a clade that is a sister group to all other Heterolobosea. We characterized the mitochondrial genomes of BB2 and P. kirbyi, which encoded 44 and 48 putative protein-coding genes respectively. Their gene contents were similar to that of Naegleria. In BB2, mitochondrially encoded RNAs were heavily edited, with ∼500 mononucleotide insertion events, mostly guanosines. These insertions always have the same identity as an adjacent nucleotide. Editing occurs in all ribosomal RNAs and protein-coding transcripts except one, and half of the transfer RNAs. Analysis of Illumina deep-sequencing data suggested that this RNA editing is very accurate and efficient, and most likely co-transcriptional. The dissimilarity of this editing process to other RNA editing phenomena in discobids, as well as its apparent absence in P. kirbyi, suggest that this remarkably extensive system of insertional editing evolved independently in the BB2 lineage, after its divergence from the P. kirbyi lineage.


Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis.
Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that are more invasive or likely to become metastatic. Despite immense information regarding Jak/STAT regulation, the signaling network has numerous missing links, which is slowing the progress towards developing drug therapies. In mammals, many components act in this cascade, with substantial cross-talk with other signaling pathways. In Drosophila, there are fewer pathway components, which has enabled significant discoveries regarding well-conserved regulatory mechanisms. Work across species illustrates the relevance of these regulators in humans. In this review, we showcase fundamental Jak/STAT regulation mechanisms in blood cells, stem cells, and cell motility. We examine the functional relevance of key conserved regulators from Drosophila to human cancer stem cells and metastasis. Finally, we spotlight less characterized regulators of Drosophila Jak/STAT signaling, which stand as promising candidates to be investigated in cancer biology. These comparisons illustrate the value of using Drosophila as a model for uncovering the roles of Jak/STAT signaling and the molecular means by which the pathway is controlled.


The vasoactive intestinal peptide receptor on intact human colonic adenocarcinoma cells (HT29-D4). Evidence for its glycoprotein nature.
We have previously shown that the mono [125I]iodinated vasoactive intestinal peptide (125I-VIP) could be covalently cross-linked on intact colonic adenocarcinoma cells (HT29). A major Mr 67,000 and a minor Mr 120,000 cross-linked polypeptides have been characterized [Muller, Luis, Fantini, Abadie, Giannellini, Marvaldi & Pichon (1985) Eur. J. Biochem. 151, 411-417]. The glycoprotein nature of these species was investigated using endo-beta-acetylglucosaminidase F (Endo F) treatment, enzymic and chemical desialylation and wheat germ agglutinin (WGA)-Sepharose affinity chromatography. Affinity-labelled VIP-binding proteins solubilized by Nonidet P-40 bound to WGA-Sepharose and could be eluted specifically with N-acetyl-D-glucosamine. Treatment with Endo F resulted in an increased electrophoretic mobility of both polypeptides. The major and the minor VIP-binding proteins were converted respectively into Mr 47,000 and 100,000 species, indicating removal of 20 kDa of N-linked oligosaccharides. Deglycosylation with trifluoromethanesulphonic acid also led to a 20 kDa loss in mass of the Mr 67,000 component, indicating the absence of additional O-linked sugars on this polypeptide. The presence of sialic acid on the major VIP-binding protein was demonstrated after treatment of intact cells with neuraminidase or by chemical desialylation with hydrochloric acid. We conclude from this study that the VIP receptor from intact HT29-D4 cells is a glycoprotein with N-linked oligosaccharide side chains containing sialic acid.


Protein design by fusion: implications for protein structure prediction and evolution.
Domain fusion is a useful tool in protein design. Here, the structure of a fusion of the heterodimeric flagella-assembly proteins FliS and FliC is reported. Although the ability of the fusion protein to maintain the structure of the heterodimer may be apparent, threading-based structural predictions do not properly fuse the heterodimer. Additional examples of naturally occurring heterodimers that are homologous to full-length proteins were identified. These examples highlight that the designed protein was engineered by the same tools as used in the natural evolution of proteins and that heterodimeric structures contain a wealth of information, currently unused, that can improve structural predictions.


[Questionnaires for assessment of work-related psychosocial hazards--a review of diagnostic tools].
Holistic management of the organization also covers psychosocial risk management. Gathering information about psychosocial work-related hazards is the first step of the psychosocial risk management. In this process, the identification of the occupational indicators on work-related stress must be done. The paper presents a review of the measures available to assess psychosocial work-related hazards which are available in Poland. The following measures are included: Psychosocial Working Conditions, Effort-Reward Imbalance (ERI), Subjective Assessment Work Characteristics Questionnaire, Objective Work Characteristics Questionnaire, HSE Indicator Tool, Brief Scale of Vocational Stress, questionnaire "Psychosocial Factors" and Questionnaire of Occupational Burdens in Teaching. Besides the basic information about the measures (e.g. scales, examples of items, psychometric parameters), critical assessment of each measure in relation to its usefulness is also provided. The main conclusion is that a well-specified goal of diagnosis and planned intervention is the key issue while choosing a questionnaire. The review of tools available in Poland can be of great help for occupational health and safety professionals, and support them in the work aimed at improvement of psychosocial working-conditions.


Binary Sensors-Based Privacy-Preserved Activity Recognition of Elderly Living Alone Using an RNN.
The recent growth of the elderly population has led to the requirement for constant home monitoring as solitary living becomes popular. This protects older people who live alone from unwanted instances such as falling or deterioration caused by some diseases. However, although wearable devices and camera-based systems can provide relatively precise information about human motion, they invade the privacy of the elderly. One way to detect the abnormal behavior of elderly residents under the condition of maintaining privacy is to equip the resident's house with an Internet of Things system based on a non-invasive binary motion sensor array. We propose to concatenate external features (previous activity and begin time-stamp) along with extracted features with a bi-directional long short-term memory (Bi-LSTM) neural network to recognize the activities of daily living with a higher accuracy. The concatenated features are classified by a fully connected neural network (FCNN). The proposed model was evaluated on open dataset from the Center for Advanced Studies in Adaptive Systems (CASAS) at Washington State University. The experimental results show that the proposed method outperformed state-of-the-art models with a margin of more than 6.25% of the F1 score on the same dataset.


Structure of the Sec13-Sec16 edge element, a template for assembly of the COPII vesicle coat.
Ancestral coatomer element 1 (ACE1) proteins assemble latticework coats for COPII vesicles and the nuclear pore complex. The ACE1 protein Sec31 and Sec13 make a 2:2 tetramer that forms the edge element of the COPII outer coat. In this study, we report that the COPII accessory protein Sec16 also contains an ACE1. The 165-kD crystal structure of the central domain of Sec16 in complex with Sec13 was solved at 2.7-A resolution. Sec16 and Sec13 also make a 2:2 tetramer, another edge element for the COPII system. Domain swapping at the ACE1-ACE1 interface is observed both in the prior structure of Sec13-Sec31 and in Sec13-Sec16. A Sec31 mutant in which domain swapping is prevented adopts an unprecedented laminated structure, solved at 2.8-A resolution. Our in vivo data suggest that the ACE1 element of Sec31 can functionally replace the ACE1 element of Sec16. Our data support Sec16 as a scaffold for the COPII system and a template for the Sec13-Sec31 coat.


Human Proteinpedia as a resource for clinical proteomics.
Clinical proteomics is an emerging field that deals with the use of proteomic technologies for medical applications. With a major objective of identifying proteins involved in pathological processes and as potential biomarkers, this field is already gaining momentum. Consequently, clinical proteomics data are being generated at a rapid pace, although mechanisms of sharing such data with the biomedical community lag far behind. Most of these data are either provided as supplementary information through journal web sites or directly made available by the authors through their own web resources. Integration of these data within a single resource that displays information in the context of individual proteins is likely to enhance the use of proteomic data in biomedical research. Human Proteinpedia is one such portal that unifies human proteomic data under a single banner. The goal of this resource is to ultimately capture and integrate all proteomic data obtained from individual studies on normal and diseased tissues. We anticipate that harnessing of these data will help prioritize experiments related to protein targets and also permit meta-analysis to uncover molecular signatures of disease. Finally, we encourage all biomedical investigators to maximize dissemination of their valuable proteomic data to rest of the community by active participation in existing repositories such as Human Proteinpedia.


Emergence of a New Highly Successful Acapsular Group A Streptococcus Clade of Genotype emm89 in the United Kingdom.
Group A Streptococcus (GAS) genotype emm89 is increasingly recognized as a leading cause of disease worldwide, yet factors that underlie the success of this emm type are unknown. Surveillance identified a sustained nationwide increase in emm89 invasive GAS disease in the United Kingdom, prompting longitudinal investigation of this genotype. Whole-genome sequencing revealed a recent dramatic shift in the emm89 population with the emergence of a new clade that increased to dominance over previous emm89 variants. Temporal analysis indicated that the clade arose in the early 1990s but abruptly increased in prevalence in 2008, coinciding with an increased incidence of emm89 infections. Although standard variable typing regions (emm subtype, tee type, sof type, and multilocus sequence typing [MLST]) remained unchanged, uniquely the emergent clade had undergone six distinct regions of homologous recombination across the genome compared to the rest of the sequenced emm89 population. Two of these regions affected known virulence factors, the hyaluronic acid capsule and the toxins NADase and streptolysin O. Unexpectedly, and in contrast to the rest of the sequenced emm89 population, the emergent clade-associated strains were genetically acapsular, rendering them unable to produce the hyaluronic acid capsule. The emergent clade-associated strains had also acquired an NADase/streptolysin O locus nearly identical to that found in emm12 and modern emm1 strains but different from the rest of the sequenced emm89 population. The emergent clade-associated strains had enhanced expression of NADase and streptolysin O. The genome remodeling in the new clade variant and the resultant altered phenotype appear to have conferred a selective advantage over other emm89 variants and may explain the changes observed in emm89 GAS epidemiology. Sudden upsurges or epidemic waves are common features of group A streptococcal disease. Although the mechanisms behind such changes are largely unknown, they are often associated with an expansion of a single genotype within the population. Using whole-genome sequencing, we investigated a nationwide increase in invasive disease caused by the genotype emm89 in the United Kingdom. We identified a new clade variant that had recently emerged in the emm89 population after having undergone several core genomic recombination-related changes, two of which affected known virulence factors. An unusual finding of the new variant was the loss of the hyaluronic acid capsule, previously thought to be essential for causing invasive disease. A further genomic adaptation in the NADase/streptolysin O locus resulted in enhanced production of these toxins. Recombination-related genome remodeling is clearly an important mechanism in group A Streptococcus that can give rise to more successful and potentially more pathogenic variants.


Comparable Outcomes for Hematologic Malignancies after HLA-Haploidentical Transplantation with Posttransplantation Cyclophosphamide and HLA-Matched Transplantation.
The implementation of high-dose posttransplantation cyclophosphamide (PTCy) has made HLA-haploidentical (haplo) blood or marrow transplantation (BMT) a cost effective and safe alternative donor transplantation technique, resulting in its increasing utilization over the last decade. We review the available retrospective comparisons of haplo BMT with PTCy and HLA-matched BMT in adults with hematologic malignancies. The examined studies demonstrate no difference between haplo BMT with PTCy and HLA-matched BMT with regard to acute graft-versus-host disease (aGVHD), nonrelapse mortality, and overall survival. Chronic GVHD occurred less frequently after haplo BMT with PTCy compared with HLA-matched BMT utilizing standard GVHD prophylaxis. In addition, patients with a high risk of relapse by the disease risk index had a suggestion of improved progression-free and overall survival after haplo BMT with PTCy when compared with a historical cohort of HLA-matched BMT in one analysis. Furthermore, in Hodgkin lymphoma relapse and progression-free survival were improved in the haplo BMT with PTCy compared with the HLA-matched BMT cohort. These findings support the use of this transplantation platform when HLA-matched related donors (MRDs) are unavailable and suggest that clinical scenarios exist in which haplo BMT may be preferred to HLA-matched BMT, which warrant further investigation.


Binding of FUN14 Domain Containing 1 With Inositol 1,4,5-Trisphosphate Receptor in Mitochondria-Associated Endoplasmic Reticulum Membranes Maintains Mitochondrial Dynamics and Function in Hearts in Vivo.
FUN14 domain containing 1 (FUNDC1) is a highly conserved outer mitochondrial membrane protein. The aim of this study is to examine whether FUNDC1 modulates the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), mitochondrial morphology, and function in cardiomyocytes and intact hearts. The impacts of FUNDC1 on MAMs formation and cardiac functions were studied in mouse neonatal cardiomyocytes, in mice with cardiomyocyte-specific Fundc1 gene knockout (Fundc1f/Y/CreαMyHC+/- ), and in the cardiac tissues of the patients with heart failure. In mouse neonatal cardiomyocytes and intact hearts, FUNDC1 was localized in MAMs by binding to ER-resided inositol 1,4,5-trisphosphate type 2 receptor (IP3R2). Fundc1 ablation disrupted MAMs and reduced the levels of IP3R2 and Ca2+ in both mitochondria and cytosol, whereas overexpression of Fundc1 increased the levels of IP3R2 and Ca2+ in both mitochondria and cytosol. Consistently, Fundc1 ablation increased Ca2+ levels in ER, whereas Fundc1 overexpression lowered ER Ca2+ levels. Further, Fundc1 ablation in cardiomyocytes elongated mitochondria and compromised mitochondrial functions. Mechanistically, we found that Fundc1 ablation-induced reduction of intracellular Ca2+ levels suppressed mitochondrial fission 1 protein (Fis1) expression and mitochondrial fission by reducing the binding of the cAMP response element binding protein (CREB) in the Fis1 promoter. Fundc1f/Y/CreαMyHC+/- mice but not their littermate control mice (Fundc1wt/Y/CreαMyHC+/- ) exhibited cardiac dysfunction. The ligation of the left ventricle artery of Fundc1f/Y/CreαMyHC+/- mice caused more severe cardiac dysfunction than those in sham-treated Fundc1f/Y/CreαMyHC+/- mice. Finally, we found that the FUNDC1/MAMs/CREB/Fis1 signaling axis was significantly suppressed in patients with heart failure. We conclude that FUNDC1 binds to IP3R2 to modulate ER Ca2+ release into mitochondria and cytosol. Further, a disruption of the FUNDC1 and IP3R2 interaction lowers the levels of Ca2+ in mitochondria and cytosol, both of which instigate aberrant mitochondrial fission, mitochondrial dysfunction, cardiac dysfunction, and heart failure.


Adaptive optical system referencing in the case of resolved targets illuminated through turbulence.
The conventional feedback of multidither outgoing-wave adaptive optical systems is inoperative in the presence of a featureless target resolved by the transmitter optics. We propose in this paper to define an artificial glint by imaging the target laser pattern on a pinhole aperture. The concept is somewhat obvious, but in turbulence the existing theory on resolution and coherence states that it is restricted to small scintillation strength. Through correlation measurements between the physical-glint return and the artificial-glint irradiance, it is shown that the range of validity is much broader than predicted. Furthermore, tests with a two-degree-of-freedom system operated in turbulence demonstrate that the artificial-glint technique allows effective convergence at propagation distances reaching far into the scintillation-saturation region, i.e., well beyond the theoretical limit.


Lymph protects metastasizing melanoma cells from ferroptosis.
Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood1-4; however, the reason for this is unclear. Here we show that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with melanomas derived from patients, and immunocompetent mice with mouse melanomas, had more melanoma cells per microlitre in tumour-draining lymph than in tumour-draining blood. Cells that metastasized through blood, but not those that metastasized through lymph, became dependent on the ferroptosis inhibitor GPX4. Cells that were pretreated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection. We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid and less free iron in lymph. Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumours. Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than did melanoma cells from subcutaneous tumours. Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood.


No influence of immigrant background on the outcome of total hip arthroplasty. 140,299 patients born in Sweden and 11,539 immigrants in the Swedish Hip Arthroplasty Register.
Total Hip Replacement (THA) is one of the most successful and cost-effective operations. Despite its benefits, marked ethnic differences in the utilization of THA are well documented. However, very little has been published on the influence of ethnicity on outcome. We investigate whether the outcome-in terms of reoperation within 2 years or revision up to 14 years after the primary operation-varies depending on ethnic background. Records of total hip arthroplasties performed between 1992 and 2007 were retrieved from the Swedish Hip Arthropalsty Registry and integrated with data on ethnicity of patients from 2 demographical databases (i.e. Patient Register and Statistics Sweden). The first operated side in patients with THA recorded in the Swedish Hip Arthroplasty Register (SHAR) between 1992 and 2007 were generally included. We excluded patients with 1 Swedish and 1 non-Swedish parent and patients born abroad with 2 Swedish parents. After these exclusions 151,838 patients were left for analysis. There were 11,539 Swedish patients born outside Sweden. We used a Cox regression model including age, sex, diagnosis, type of fixation, whether or not there was comorbidity according to Elixhauser or not, marital status and educational level. The mean age was lowest in the group of patient coming from outside Europe including the former Soviet Union (61 years), and highest in the Swedish population (70 years). Before adjustment, for covariates, patients born in Europe outside the Nordic countries showed a lower risk to undergo early reoperation (HR = 0.73, 95% CI: 0.56-0.97), which increased after adjustment to (HR = 0.76, 95% CI: 0.58-1.01). Before adjustment, patients born in the Nordic countries outside Sweden and those born outside Europe (including the former Soviet Union) showed a higher risk to undergo revision than patients born in Sweden (HR = 1.14, 95% CI: 1.02-1.27; HR = 1.49, 95% CI: 1.2-1.9), but this difference disappeared after adjustment for covariates. We did not find any certain differences in reoperation within 2 years, or revision within 14 years, between patients born in Sweden and immigrants. Further studies are needed to determine whether our observations are biased by the attitude of health providers regarding performance of these procedures, or by a reluctance of certain patient groups to seek medical attention should any complications requiring reoperation or revision occur.


Brain metastases in children with melanoma.
Brain metastases complicate the course of malignant melanoma in at least 20% of adult cases. These events are commonly preceded by metastases to other sites. Due to the rarity of malignant melanoma in children, little is known about the incidence, clinical features, and outcome of children with melanoma who develop brain metastases. The authors reviewed the records of 44 children with malignant melanoma treated at St. Jude Children's Research Hospital over a 33-year period. Eight (18%) developed brain metastases during the course of their disease. The authors reviewed the clinical and radiologic features of six of these cases, for whom complete clinical information and imaging studies were available. The median age at diagnosis of malignant melanoma was 15 years (range, 11-21 years). Brain metastases developed a median of 20 months (range, 0-50 months) after diagnosis and were preceded by metastases to other organs in 5 patients. In most cases, lesions were supratentorial and multiple. Most showed radiologic signs of intralesional hemorrhage. All patients received whole brain radiotherapy, and one had surgical resection. Three patients received chemotherapy. Five patients died a median of 5 months (range, 2-10 months) after diagnosis of brain involvement. One patient, who had a single brain metastasis at diagnosis, is alive more than 34 months later. Brain metastases develop in a significant proportion of children with malignant melanoma and are associated with a poor outcome. The incidence, features, and outcome in children do not appear to differ from those in adults.


Investigation of donor KIR content and matching in children undergoing hematopoietic cell transplantation for acute leukemia.
Multiple models of donor killer immunoglobulin receptor (KIR) alloreactivity or KIR genotype have been reported to be protective against leukemia relapse after allogeneic transplantation. However, few studies have addressed this topic in the pediatric population. Here, we assessed the outcomes of allogeneic transplantation in children with acute lymphoblastic leukemia (ALL; n = 372) or acute myeloid leukemia (AML; n = 344) who received unrelated donor (URD) transplantation and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2005 to 2016. As expected in this pediatric population, most patients underwent myeloablative conditioning while in remission and with bone marrow as a stem cell source. We tested KIR ligand mismatch, KIR gene content (centromeric [Cen] B), KIR2DS1 mismatching, and Cen B/telomeric A using Cox regression models and found that none were significantly associated with either relapse or disease-free survival when considering the entire cohort of patients (ALL and AML), AML, or ALL separately. Moreover, there was no significant association with outcomes in the in vivo T-cell-depleted (ie, serotherapy) cohort. This study, which is the largest analysis of donor KIR in the pediatric acute leukemia population, does not support the use of KIR in the selection of URDs for children undergoing T-replete transplantation.


Design and implementation of a prototype radiotherapy menu in a patient portal.
Radiotherapy patients often face undue anxiety due to misconceptions about radiation and their inability to visualize their upcoming treatments. Access to their personal treatment plans is one way in which pre-treatment anxiety may be reduced. But radiotherapy data are quite complex, requiring specialized software for display and necessitating personalized explanations for patients to understand them. Therefore, our goal was to design and implement a novel radiotherapy menu in a patient portal to improve patient access to and understanding of their radiotherapy treatment plans. A prototype radiotherapy menu was developed in our institution's patient portal following a participatory stakeholder co-design methodology. Customizable page templates were designed to render key radiotherapy data in the portal's patient-facing mobile phone app. DICOM-RT data were used to provide patients with relevant treatment parameters and generate pre-treatment 3D visualizations of planned treatment beams, while the mCODE data standard was used to provide post-treatment summaries of the delivered treatments. A focus group was conducted to gather initial patient feedback on the menu. Pre-treatment: the radiotherapy menu provides patients with a personalized treatment plan overview, including a personalized explanation of their treatment, along with an interactive 3D rendering of their body, and treatment beams for visualization. Post-treatment: a summary of the delivered radiotherapy is provided, allowing patients to retain a concise personal record of their treatment that can easily be shared with future healthcare providers. Focus group feedback was overwhelmingly positive. Patients highlighted how the intuitive presentation of their complex radiotherapy data would better prepare them for their radiation treatments. We successfully designed and implemented a prototype radiotherapy menu in our institution's patient portal that improves patient access to and understanding of their radiotherapy data. We used the mCODE data standard to generate post-treatment summaries in a way that is easily shareable and interoperable.


Negligible genetic diversity of mycobacterium tuberculosis host immune system protein targets: evidence of limited selective pressure.
A common theme in medical microbiology is that the amount of amino acid sequence variation in proteins that are targets of the host immune system greatly exceeds that found in metabolic enzymes or other housekeeping proteins. Twenty-four Mycobacterium tuberculosis genes coding for targets of the host immune system were sequenced in 16 strains representing the breadth of genomic diversity in the species. Of the 24 genes, 19 were invariant and only six polymorphic nucleotide sites were identified in the 5 genes that did have variation. The results document the highly unusual circumstance that prominent M. tuberculosis antigenic proteins have negligible structural variation worldwide. The data are best explained by a combination of three factors: (i) evolutionarily recent global dissemination in humans, (ii) lengthy intracellular quiescence, and (iii) active replication in relatively few fully immunocompetent hosts. The very low level of amino acid diversity in antigenic proteins may be cause for optimism in the difficult fight to control global tuberculosis.


Nasogastric or nasojejunal feeding in predicted severe acute pancreatitis: a meta-analysis.
Enteral feeding can be given either through the nasogastric or the nasojejunal route. Studies have shown that nasojejunal tube placement is cumbersome and that nasogastric feeding is an effective means of providing enteral nutrition. However, the concern that nasogastric feeding increases the chance of aspiration pneumonitis and exacerbates acute pancreatitis by stimulating pancreatic secretion has prevented it being established as a standard of care. We aimed to evaluate the differences in safety and tolerance between nasogastric and nasojejunal feeding by assessing the impact of the two approaches on the incidence of mortality, tracheal aspiration, diarrhea, exacerbation of pain, and meeting the energy balance in patients with severe acute pancreatitis. We searched the electronic databases of the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We included prospective randomized controlled trials comparing nasogastric and nasojejunal feeding in patients with predicted severe acute pancreatitis. Two reviewers assessed the quality of each study and collected data independently. Disagreements were resolved by discussion among the two reviewers and any of the other authors of the paper. We performed a meta-analysis and reported summary estimates of outcomes as Risk Ratio (RR) with 95% confidence intervals (CIs). We included three randomized controlled trials involving a total of 157 patients. The demographics of the patients in the nasogastric and nasojejunal feeding groups were comparable. There were no significant differences in the incidence of mortality (RR=0.69, 95% CI: 0.37 to 1.29, P=0.25); tracheal aspiration (RR=0.46, 95% CI: 0.14 to 1.53, P=0.20); diarrhea (RR=1.43, 95% CI: 0.59 to 3.45, P=0.43); exacerbation of pain (RR=0.94, 95% CI: 0.32 to 2.70, P=0.90); and meeting energy balance (RR=1.00, 95% CI: 0.92 to 1.09, P=0.97) between the two groups. Nasogastric feeding was not inferior to nasojejunal feeding. Nasogastric feeding is safe and well tolerated compared with nasojejunal feeding. Study limitations included a small total sample size among others. More high-quality large-scale randomized controlled trials are needed to validate the use of nasogastric feeding instead of nasojejunal feeding.


The neuronal network of laughing in young patients with untreated narcolepsy.
To investigate the neuronal correlates of spontaneous laughter in drug-naive pediatric patients with narcolepsy type I (NT1) compared to healthy controls by means of blood oxygen level-dependent (BOLD) MRI. Twenty-one children/adolescents with recent onset of NT1 and 21 age- and sex-matched healthy controls were studied with fMRI while viewing funny videos using a naturalistic paradigm. Whole-brain hemodynamic correlates of spontaneous laughter were investigated in each group and compared by use of appropriate second-level general linear model analyses. If recorded, cataplexy events were treated as the effect of no interest at the single-participant level. Correlations analyses between these contrasts and behavioral findings were performed. Emotion-induced laughter occurred in 16 patients (294 events) and 21 controls (357 events). In controls, laughter-related BOLD increases involved a widespread cortical and subcortical network including the bilateral motor and premotor areas, cingulated cortex, insula, and amygdala. In NT1, laughter induced BOLD signal increments in the motor cortex, right thalamus, and left subthalamic nucleus/zona incerta (STN/ZI). STN/ZI and thalamic changes were significantly higher during fMRI sessions with laughter without cataplexy compared to sessions in which laughter was associated with cataplexy. Laughter expression in individuals with NT1 involves different brain circuits compared to controls by means of overactivation of cortical and subcortical regions belonging to the volitional control of laughter. The activation of the STN/ZI region observed predominantly in patients with NT1 during laugh episodes without cataplexy suggests that the ZI could act to prevent cataplexy.


Uptake of NO-releasing drugs by the P2 nucleoside transporter in trypanosomes.
Nitric oxide (NO.) has been identified as a principal regulatory molecule of the immune system and the major cytotoxic mediator of activated immune cells. NO. can also react rapidly with a variety of biological species, particularly with the superoxide radical anion O2.- at almost diffusion-limited rates to form peroxynitrite anion (ONOO-). ONOO- and its proton-catalyzed decomposition products are capable of oxidizing a great diversity of biomolecules and can act as a source of toxic hydroxyl radicals. As a consequence, a strategy for the development of molecules with potential trypanocidal activities could be developed to increase the concentration of nitric oxide in the parasites through NO.-releasing compounds. In this way, the rate of formation of peroxynitrite from NO. and O2.- would be faster than the rate of dismutation of superoxide radicals by superoxide dismutases which constitute the primary antioxidant enzymatic defense system in trypanosomes. The adenosine transport systems of parasitic protozoa, which are also in certain cases implicated in the selective uptake of active drugs such as melarsoprol or pentamidine, could be exploited to specifically target these NO.-releasing compounds inside the parasites. In this work, we present the synthesis, characterization and biological evaluation of a series of molecules that contain both a group which would specifically target these drugs inside the parasites via the purine transporter, and an NO.-donor group that would exert a specific pharmacological effect by increasing NO level, and thus the peroxynitrite concentration inside the parasite.


Acetylation of beta-catenin by p300 regulates beta-catenin-Tcf4 interaction.
Lysine acetylation modulates the activities of nonhistone regulatory proteins and plays a critical role in the regulation of cellular gene transcription. In this study, we showed that the transcriptional coactivator p300 acetylated beta-catenin at lysine 345, located in arm repeat 6, in vitro and in vivo. Acetylation of this residue increased the affinity of beta-catenin for Tcf4, and the cellular Tcf4-bound pool of beta-catenin was significantly enriched in acetylated form. We demonstrated that the acetyltransferase activity of p300 was required for efficient activation of transcription mediated by beta-catenin/Tcf4 and that the cooperation between p300 and beta-catenin was severely reduced by the K345R mutation, implying that acetylation of beta-catenin plays a part in the coactivation of beta-catenin by p300. Interestingly, acetylation of beta-catenin had opposite, negative effects on the binding of beta-catenin to the androgen receptor. Our data suggest that acetylation of beta-catenin in the arm 6 domain regulates beta-catenin transcriptional activity by differentially modulating its affinity for Tcf4 and the androgen receptor. Thus, our results describe a new mechanism by which p300 might regulate beta-catenin transcriptional activity.


Esophageal SpO2 measurements from a pediatric burns-patient: a case study.
Pulse oximetry is being used in everyday clinical practice in anesthesia utilizing peripheral saturation sensors. However, it may be unreliable in certain clinical situations such as peripheral hypoperfusion. Similar situations occur in burns patients and more importantly burns to extremities which limit the sites available for measurement of peripheral oxygen saturation (SpO2). To overcome these limitations, the esophagus has been investigated as an alternative measurement site, as perfusion may be preferentially preserved centrally. A miniaturized reflectance esophageal saturation (SpO2 probe has been constructed utilizing infrared and red photodiodes and a photodetector. Our case study was aimed at evaluating the reliability of esophageal pulse oximetry in a major burns infant. Measurable photoplethysmographic (PPG) traces and SpO2 values were obtained in the neonatal esophagus. It was found that the esophageal pulse oximeter results were in good agreement with oxygen saturation measurements obtained by a commercial ear lobe pulse oximeter. This study suggests that the esophagus can be used as an alternative site for monitoring arterial blood oxygen saturation by pulse oximetry in burned infants.


Increase in Daily Steps After an Exercise Specialist Led Lifestyle Intervention for Adults With Type 2 Diabetes In Primary Care: A Controlled Implementation Trial.
To determine the effectiveness of an exercise specialist led lifestyle program for adults with type 2 diabetes in primary care. Eligible participants from 4 primary care networks in Alberta, Canada were assigned to either a lifestyle program or a control group. The program targeted increased daily walking through individualized daily pedometer step goals for the first 3 months and brisk walking speed, along with substitution of low-relative to high-glycemic index foods over the next 3 months. The outcomes were daily steps, diet, and clinical markers, and were compared using random effects models. 198 participants were enrolled (102 in the intervention and 96 in the control). For all participants, (51% were women), mean age 59.5 (SD 8.3) years, A1c 6.8% (SD 1.1), BMI 33.6 kg/m(2) (SD 6.5), systolic BP 125.6 mmHg (SD 16.2), glycemic index 51.7 (4.6), daily steps 5879 (SD 3130). Daily steps increased for the intervention compared with the control at 3-months (1292 [SD 2698] vs. 418 [SD 2458] and 6-months (1481 [SD 2631] vs. 336 [SD 2712]; adjusted P = .002). No significant differences were observed for diet or clinical outcomes. A 6-month lifestyle program delivered in primary care by an exercise specialist can be effective for increasing daily walking among adults with recently diagnosed type 2 diabetes. This short-term increase in daily steps requires longer follow-up to estimate the potential impact on health outcomes.


Vertical transmission of hepatitis C virus: systematic review and meta-analysis.
We conducted a systematic review of estimates of hepatitis C virus (HCV) vertical transmission risk to update current estimates published more than a decade ago. PubMed and Embase were searched and 109 articles were included. Pooled estimates of risk were generated for children born to HCV antibody-positive and viremic women, aged ≥18 months, separately by maternal human immunodeficiency virus (HIV) coinfection. Meta-analysis of the risk of vertical HCV infection to children of HCV antibody-positive and RNA-positive women was 5.8% (95% confidence interval [CI], 4.2%-7.8%) for children of HIV-negative women and 10.8% (95% CI, 7.6%-15.2%) for children of HIV-positive women. The adjusted meta-regression model explained 51% of the between-study variation in the 25 included risk estimates. Maternal HIV coinfection was the most important determinant of vertical transmission risk (adjusted odds ratio, 2.56 [95% CI, 1.50-4.43]). Additional methodological (follow-up rate and definition of infection in children) and risk factors independently predicted HCV infection and need to be captured and reported by future studies of vertical transmission. Studies assessing the contribution of nonvertical exposures in early childhood to HCV prevalence among children at risk of vertical transmission are needed. More than 1 in every 20 children delivered by HCV chronically infected women are infected, highlighting that vertical transmission likely constitutes the primary transmission route among children. These updated estimates are a basis for decision making in prioritization of research into risk-reducing measures, and inform case management in clinical settings, especially for HIV-positive women in reproductive age.


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S. Taïeb, L. Ceugnart, F. Bonodeau, L. Vanseymortier, A. Adenis The management and the prognosis of gastrointestinal stromal tumors (GIST) have evolved rapidly with new targeted treatments. The aim of this paper is to assess the role of imaging not only for diagnosis but to quantify treatment response. RECIST criteria, which are the standard in assessment of post chemotherapy response in adult's solid tumors, can not be used in targeted therapy: the changes in lesion structures even if case of increasing volume are more specific to assess tumor response.


Causes of blindness and visual impairment at the school for the blind owo, Nigeria.
This study was designed to determine the causes of blindness amongst the pupils of the School for the blind ,Owo and also identify treatable causes of blindness in the study population. This study was conducted between November and December,2007 at the School for the blind, Owo. Ethical clearance was obtained from the Ethical Committee of Federal Medical Centre, Owo prior to carrying out this study. Sixty two pupils of the School for the blind and blind students in Owo High school were enrolled in this study. The subjects were interviewed and examined by the authors with the aid of WHO'S recording form for blindness and visual impairment in children. The data obtained with the study instrument was collated and analyzed with SPSS 12.0.1. MAJORITY OF THE SUBJECTS: 55 (88.7%) were blind while the remaining 7 (11.3%) had low vision. Lens ranked highest amongst the anatomical sites of visual loss accounting for 24.2%,followed by retina (14.5%),optic nerve (12.9%) and glaucoma (12.9%).The main aetiological factors were intrauterine (37.1%) and hereditary factors (21%). The commonest single diagnosis was cataract (21%) followed by glaucoma (12.9%). Twenty seven respondents (43.6%) had treatable causes of blindness. The lens ranked highest amongst the anatomical sites of blindness and visual impairment. The main aetiological factors were intrauterine and hereditary factors. The commonest single diagnosis was cataract. Less than half of the respondents had treatable causes of blindness and visual impairment.


The influence of dissolved oxygen on winter habitat selection by largemouth bass: an integration of field biotelemetry studies and laboratory experiments.
In this study, field biotelemetry and laboratory physiology approaches were coupled to allow understanding of the behavioral and physiological responses of fish to winter hypoxia. The biotelemetry study compared dissolved oxygen levels measured throughout the winter period with continually tracked locations of nine adult largemouth bass obtained from a whole-lake submerged telemetry array. Fish habitat usage was compared with habitat availability to assess whether fish were selecting for specific dissolved oxygen concentrations. The laboratory study examined behavioral and physiological responses to progressive hypoxia in juvenile largemouth bass acclimated to winter temperatures. Results from the dissolved oxygen measurements made during the biotelemetry study showed high variance in under-ice dissolved oxygen levels. Avoidance of water with dissolved oxygen <2.0 mg/L by telemetered fish was demonstrated, but significant use of water with intermediate dissolved oxygen levels was also found. Results from the lab experiments showed marked changes in behavior (i.e., yawning and vertical movement) at <2.0 mg/L of dissolved oxygen but no change in tissue lactate, an indicator of anaerobic metabolism. Combined results of the biotelemetry and laboratory studies demonstrate that a dissolved oxygen content of 2.0 mg/L may be a critical threshold that induces behavioral responses by largemouth bass during the winter. In addition, the use by fish of areas with intermediate levels of dissolved oxygen suggests that there are multiple environmental factors influencing winter behavior.


Impact of energetic-particle-driven geodesic acoustic modes on turbulence.
The impact on turbulent transport of geodesic acoustic modes excited by energetic particles is evidenced for the first time in flux-driven 5D gyrokinetic simulations using the Gysela code. Energetic geodesic acoustic modes (EGAMs) are excited in a regime with a transport barrier in the outer radial region. The interaction between EGAMs and turbulence is such that turbulent transport can be enhanced in the presence of EGAMs, with the subsequent destruction of the transport barrier. This scenario could be particularly critical in those plasmas, such as burning plasmas, exhibiting a rich population of suprathermal particles capable of exciting energetic modes.


Biosynthesis and characterization of mercury sulphide nanoparticles produced by Bacillus cereus MRS-1.
Mercury is a highly toxic heavy metal accumulated in the environment, which can be detoxified by reducing Hg2+ to non toxic form. Bacteria resistant to toxic metals and capable of converting them into non toxic forms have a direct application in the bioremediation of contaminated sites. In this study, mercury resistant strain Bacillus cereus MRS-1 was isolated from electroplating industrial effluent. This strain exhibited the ability to convert mercury into extracellular sulphide nanoparticles of mercury. The recovered HgS nanoparticles have been characterized by UV-VIS spectrophotometer, FT-IR, atomic force microscopy, transmission electron microscopy, scanning electron microscopy, energy dispersive X-ray analysis, powder X-ray diffraction pattern and thermogravimetric analysis. The synthesized nanoparticles were spherical with a size range of 10-100 nm. This strain can be potentially exploited for the production of HgS nanoparticles as well as for detoxification of mercury in the environment without producing secondary pollution of mercury methylation or Hg (0) volatilization.


Maltreatment subtypes, depressed mood, and anhedonia: A longitudinal study with adolescents.
Maltreatment exposure is a robust predictor of adolescent depression. Yet despite this well-documented association, few studies have simultaneously examined how maltreatment subtypes relate to qualitatively distinct depressive symptoms. The present multiwave longitudinal study addressed this gap in the literature by examining how different maltreatment subtypes independently impact depressed mood and anhedonia over time in a diverse adolescent sample. Adolescents (N = 673, Mage = 14.83, SDage = 0.66, 57.1% female, 32.8% Hispanic, 30.4% Caucasian, 25.0% African American) completed self-report inventories for child-maltreatment and annual self-report measures of depressed mood and anhedonia over the course of 6 years. We used latent-growth-curve modeling to test how maltreatment exposure predicted anhedonia and depressed mood, and whether these relations differed as a function of sex and/or race/ethnicity. Overall, both emotional abuse (p < .001) and neglect (p = .002) predicted levels of depressed mood over time, whereas only emotional neglect predicted levels (p < .001) and trajectories (p = .001) of anhedonia. Physical and sexual abuse did not predict depressive symptoms after accounting for emotional abuse and neglect (ns). These findings were largely invariant across sex and race. Findings suggest that the consequences of emotional neglect may be especially problematic in adolescence because of its impact on both depressed mood and anhedonia, and that emotional abuse's association with depression is best explained via symptoms of depressed mood. These findings are congruent with recent findings that more "silent types" of maltreatment uniquely predict depression, and that abuse and neglect experiences confer distinct profiles of risk for psychological distress. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Measurement Efficiency for Fixed-Precision Multidimensional Computerized Adaptive Tests: Comparing Health Measurement and Educational Testing Using Example Banks.
It is currently not entirely clear to what degree the research on multidimensional computerized adaptive testing (CAT) conducted in the field of educational testing can be generalized to fields such as health assessment, where CAT design factors differ considerably from those typically used in educational testing. In this study, the impact of a number of important design factors on CAT performance is systematically evaluated, using realistic example item banks for two main scenarios: health assessment (polytomous items, small to medium item bank sizes, high discrimination parameters) and educational testing (dichotomous items, large item banks, small- to medium-sized discrimination parameters). Measurement efficiency is evaluated for both between-item multidimensional CATs and separate unidimensional CATs for each latent dimension. In this study, we focus on fixed-precision (variable-length) CATs because it is both feasible and desirable in health settings, but so far most research regarding CAT has focused on fixed-length testing. This study shows that the benefits associated with fixed-precision multidimensional CAT hold under a wide variety of circumstances.


Utilising a simulation platform to understand the effect of domain model assumptions.
Computational and mathematical modelling approaches are increasingly being adopted in attempts to further our understanding of complex biological systems. This approach can be subjected to strong criticism as substantial aspects of the biological system being captured are not currently known, meaning assumptions need to be made that could have a critical impact on simulation response. We have utilised the CoSMoS process in the development of an agent-based simulation of the formation of Peyer's patches (PP), gut-associated lymphoid organs that have a key role in the initiation of adaptive immune responses to infection. Although the use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insight into the cellular components and associated pathways involved in PP development, interesting questions remain that cannot be addressed using these approaches, and as such well justified assumptions have been introduced into our model to counter this. Here we focus not on the development of the model itself, but instead demonstrate how the resultant simulation can be used to assess how these assumptions impact the simulation response. For example, we consider the impact of our assumption that the migration rate of lymphoid tissue cells into the gut remains constant throughout PP development. We demonstrate that an analysis of the assumptions made in the construction of the domain model may either increase confidence in the model as a representation of the biological system it captures, or may suggest areas where further biological experimentation is required.


The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass.
Mechanistic target of rapamycin complex 1 (mTORC1) deficiency or chronic hyperactivation in pancreatic β-cells leads to diabetes. mTORC1 complexes with La-related protein 1 (LARP1) to specifically regulate the expression of 5' terminal oligopyrimidine tract (5'TOP) mRNAs which encode proteins of the translation machinery and ribosome biogenesis. Here we show that LARP1 is the most expressed LARP in mouse islets and human β-cells, being 2-4-fold more abundant than LARP1B, a member of the family that also interacts with mTORC1. Interestingly, β-cells from diabetic patients have higher LARP1 and LARP1B expression. However, specific deletion of Larp1 gene in β-cells (β-Larp1KO mice) did not impair insulin secretion and glucose metabolism in male and female mice. High fat or high branched-chain amino acid (BCAA) diets did not disturb glucose homeostasis compared to control littermates up to 8 weeks; BCAA diet slightly impaired glucose tolerance in the β-Larp1KO mice at 16 weeks. However, no differences in plasma insulin levels, non-fasting glycemia and β-cell mass were observed in the β-Larp1KO mice. In conclusion, LARP1 is the most abundant LARP in mouse islets and human β-cells, and it is upregulated in diabetic subjects. However, genetically disruption of Larp1 gene did not impact glucose homeostasis in basal and diabetogenic conditions, suggesting no major role for LARP1 in β-cells.


Specificity of a BCG-induced pulmonary granulomatous response in rabbits.
The specificity of Bacillus Calmette Guérin (BCG)-induced accelerated pulmonary granuloma formation has been evaluated in rabbits by cross sensitization-challenge experiments by using another granulomagenic organism, Corynebacterium granulosum. BCG-sensitized rabbits responded to challenge with homologous but not heterologous antigen, indicating that BCG-induced accelerated granuloma formation displays specificity characteristic of immunological reactions. These differences were also observed in local pulmonary delayed hypersensitivity, as determined by the migration inhibition test. The relationship between local pulmonary delayed hypersensitivity and the accelerated granulomatous response is discussed.


Formation and reduction of aryl and heterocyclic nitroso compounds and significance in the flux of hydroxylamines.
Cytochrome p450 (p450) 1A2 and NADPH-P450 reductase (NPR) catalyzed the oxidation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), with consumption of NADPH. The oxidation rate of NADPH by p450 1A2/NPR increased with time in the presence of IQ until depletion of NADPH. This unusual autocatalytic pattern of NADPH oxidation could be rationalized by formation of a nitroso derivative (IQ-N=O) and the subsequent reduction of the hydroxylamine (IQ-NHOH) and IQ-N=O, which would consume more NADPH. The formation of IQ-NHOH and IQ-N=O from IQ was confirmed using HPLC/MS. Reduction of IQ-NHOH and IQ-N=O was NPR-dependent but did not require p450. Autocatalytic NADPH oxidation was also observed in the oxidation of other heterocyclic and arylamines. However, the N-hydroxyl and nitroso oxidation products of 2-aminofluorene and 4-aminobiphenyl were reduced nonenzymatically by NADPH, and NPR did not catalyze the reactions. We simulated the enzymatic kinetic model for possible pathways for IQ metabolism, which included the formation of IQ-N=O, using some kinetic parameters obtained from the experimental results. In the kinetic model, we could reproduce the similar curvature for NADPH oxidation and the formation of IQ-N=O, and the reduction of IQ-NHOH and IQ-N=O is required to explain the observed results for NADPH oxidation. Our results support a role for nitroso derivatives of HAAs in the unusual autocatalytic NADPH oxidation and may have relevance in terms of possible toxicities of the nitroso derivatives. Both IQ-NHOH and IQ-N=O were mutagenic in a bacterial tester system devoid of p450 and NPR; the mutagenicity of both was decreased by expression of NPR, consistent with the reduction of these compounds observed with purified NPR.


Epidemiology of Plasmodium and Helminth Coinfection and Possible Reasons for Heterogeneity.
Understanding the impact of helminth infections on clinical malaria is useful for designing effective malaria control strategies. Plenty of epidemiological studies have been conducted to unravel the nature of interactions between Plasmodium and helminth infection. Careful broad summarization of the existing literature suggests that Schistosoma mansoni and hookworm infections may increase the risk of clinical malaria and associated morbidities, but Trichuris trichiura infection is not associated with the occurrence of clinical malaria and related outcomes. However, findings about effect of Ascaris lumbricoides and Schistosoma haematobium infection on clinical malaria are contradictory. Furthermore, the nature of relationship of helminth infection with severe malaria has also not been determined with certainty. This review summarizes the findings of epidemiological studies of Plasmodium and helminth coinfection, placing greater emphasis on the impact of the coinfection on malaria. Possible reasons for the heterogeneity of the findings on malaria and helminth coinfections are also discussed.


Effect of Asymmetry on the Contact Time of Droplet Impact on Superhydrophobic Cylindrical Surfaces.
Reducing the contact time during the droplet impact on the surface is crucial for anti-icing, self-cleaning, and heat transfer optimization applications. This study aims to minimize the contact time by modifying the surface curvature to create an asymmetric impact process. Our experiments showed that the increase in Weber numbers (We) and the decrease in the ratio of surface diameter to droplet diameter (D*) intensify the asymmetry of the impact process, yielding four distinct rebound modes. Low asymmetry observes the liquid retract toward the central point (Rebound Modes 1 and 2), whereas high asymmetry yields a wing-like rebound (Rebound Modes 3 and 4). In Rebound Mode 1, increased asymmetry would lead to more extended contact due to the prolonged waiting period. Conversely, the reduction in contact time in Rebound Mode 2 occurs due to increased asymmetry with no waiting period. For Rebound Modes 3 and 4, the retraction time could be divided into three stages, generated by two liquid detachment modes from the surface. Analysis reveals that an increased asymmetry would reduce the retraction time during the first stage but prolong it during the third stage, with no significant effects on the second. Four correlations, each pertaining to a distinct impact mode, are proposed based on these analyses to describe the contact time concerning We and D* for droplets impacting a superhydrophobic cylindrical surface.


LCAO approximation for scaling properties of the Menger sponge fractal.
The electromagnetic eigenmodes of a three-dimensional fractal called the Menger sponge were analyzed by the LCAO (linear combination of atomic orbitals) approximation and a first-principle calculation based on the FDTD (finite-difference time-domain) method. Due to the localized nature of the eigenmodes, the LCAO approximation gives a good guiding principle to find scaled eigenfunctions and to observe the approximate self-similarity in the spectrum of the localized eigenmodes.


Effects of nicotinic acid on plasma volume loss of experimental dysbarism.
Two groups of dogs anesthetized with sodium pentobarbital were subjected to compression of 60 psig for 60 min and decompressed at the rate of 10 psi/min without staging. Plasma volume was measured in each group by I131-tagged albumin dilution technique prior to compression, 10 min and 60 min after decompression. One group of animals received no other treatment and the other group received 15 mg/kg of body weight of nicotinic acid by intravenous injection immediately prior to compression and an additional 7.5 mg/kg of body weight of nicotinic acid 30 min after decompression. Both the untreated and the nicotinic acid-treated animals lost significant plasma volume at both the 10- and 60-min postdecompression measurements. Nicotinic acid-treated animals lost significantly less plasma.


"Just Because You Have Ears Doesn't Mean You Can Hear"-Perception of Racial-Ethnic Discrimination During Childbirth.
Black and Latina women in New York City are twice as likely to experience a potentially life-threatening morbidity during childbirth than White women. Health care quality is thought to play a role in this stark disparity, and patient-provider communication is one aspect of health care quality targeted for improvement. Perceived health care discrimination may influence patient-provider communication but has not been adequately explored during the birth hospitalization. Our objective was to investigate the impact of perceived racial-ethnic discrimination on patient-provider communication among Black and Latina women giving birth in a hospital setting. We conducted four focus groups of Black and Latina women (n=27) who gave birth in the past year at a large hospital in New York City. Moderators of concordant race/ethnicity asked a series of questions on the women's experiences and interactions with health care providers during their birth hospitalizations. One group was conducted in Spanish. We used an integrative analytic approach. We used the behavioral model for vulnerable populations adapted for critical race theory as a starting conceptual model. Two analysts deductively coded transcripts for emergent themes, using constant comparison method to reconcile and refine code structure. Codes were categorized into themes and assigned to conceptual model categories. Predisposing patient factors in our conceptual model were intersectional identities (eg, immigrant/Latina or Black/Medicaid recipient), race consciousness ("…as a woman of color, if I am not assertive, if I am not willing to ask, then they will not make an effort to answer"), and socially assigned race (eg, "what you look like, how you talk"). We classified themes of differential treatment as impeding factors, which included factors overlooked in previous research, such as perceived differential treatment due to the relationship with the infant's father and room assignment. Themes for differential treatment co-occurred with negative provider communication attributes (eg, impersonal, judgmental) or experience (eg, not listened to, given low priority, preferences not respected). Perceived racial-ethnic discrimination during childbirth influences patient-provider communication and is an important and potentially modifiable aspect of the patient experience. Interventions to reduce obstetric health care disparities should address perceived discrimination, both from the provider and patient perspectives.


Clinical measures of gestational age in normal pregnancies.
Obstetric findings in 89 healthy women were evaluated prospectively by one obstetrician unaware of menstrual history. With weekly examinations, fetal heart tones were audible by fetoscope at 17.1 +/- 1.1 weeks' gestation (mean +/- SD) and the fundus reached the umbilicus at 16.6 +/- 0.9 weeks. At 20 to 31 weeks, fundal height in centimeters equaled weeks' gestation (confidence interval: +/- 3 weeks). The accuracy of predicting delivery date from combined findings (SD: 11.4 days) approached that from reliable menstrual history (SD: 10.2 days). Gestational age at delivery minus the pediatric Dubowitz estimate was 0.4 +/- 1.7 weeks. Gestational age may be overestimated by up to six weeks by assuming that the fundus reaches the umbilicus or that fetal heart tones appear at 20 weeks. However, carefully derived obstetric estimates potentially may be more reliable than pediatric estimates.


Odour signals major histocompatibility complex genotype in an Old World monkey.
The major histocompatibility complex (MHC) is an extraordinarily diverse cluster of genes that play a key role in the immune system. MHC gene products are also found in various body secretions, leading to the suggestion that MHC genotypes are linked to unique individual odourtypes that animals use to assess the suitability of other individuals as potential mates or social partners. We investigated the relationship between chemical odour profiles and genotype in a large, naturally reproducing population of mandrills, using gas chromatography-mass spectrometry and MHC genotyping. Odour profiles were not linked to the possession of particular MHC supertypes. Sex influenced some measures of odour diversity and dominance rank influenced some measures of odour diversity in males, but not in females. Odour similarity was strongly related to similarity at the MHC, and, in some cases, to pedigree relatedness. Our results suggest that odour provides both a cue of individual genetic quality and information against which the receiver can compare its own genotype to assess genetic similarity. These findings provide a potential mechanism underlying mate choice for genetic diversity and MHC similarity as well as kin selection.


Flourishing or Languishing? The Relationship Between Mental Health, Health Locus of Control and Generalised Self-Efficacy.
Mental health is a core component of overall wellbeing and can contribute to positive functioning and purpose in life. Mental health is purportedly related to the constructs of generalised self-efficacy (GSE) and health locus of control (LOC). Most research, however, has explored GSE and LOC and their relationship with psychopathology, or defined mental health as a lack of psychopathology indicators. This contradicts the two continua model of mental health, as it does not incorporate positive mental functioning. The current study sought to re-examine the relationship between health LOC, GSE, and mental health, whilst controlling for potential confounding factors. It was anticipated that health LOC and GSE would predict mental health. A sample of 224 adults completed an online survey comprised of validated psychometric tools scales. Regression analyses were conducted to determine whether health LOC and GSE predicted mental health, after controlling for self-esteem, social support, and coping. Results indicated that GSE was a significant unique positive predictor of mental health. Health locus of control was not a significant predictor of mental health. Limitations were present, including a cross-sectional research design and use of convenience sampling. This study builds upon existing research in providing a better understanding of contributors to mental health, which may assist in the development of evidence-based mental health promotion interventions.


Effect of pH on the control release of microencapsulated dye in lecithin liposomes. II.
The objective of our work has been the microencapsulation of dyes with lecithin from soybean, with the formation of liposomes, as a substitute for synthetic auxiliaries so as to improve the quality of the effluent. Current scenarios promote the disintegration and leakage of the liposomes, such as, changes in temperature, pH, and the use of surfactants. Since dyeing process is a mix of all these parameters, we pretended to study each one separately. Changes in pH at constant temperature induce a release of dye similar with changes in temperature. In acid conditions, we found a very fast initial dye release which doesn't occur in basic conditions. Using carboxyfluorescein, as a pH fluorescence probe, we concluded that the liposome membrane doesn't protect the liposome interior from changes on the external pH.


Halogenated Organic Compounds Identified in Hydraulic Fracturing Wastewaters Using Ultrahigh Resolution Mass Spectrometry.
Large volumes of water return to the surface following hydraulic fracturing of deep shale formations to retrieve oil and natural gas. Current understanding of the specific organic constituents in these hydraulic fracturing wastewaters is limited to hydrocarbons and a fraction of known chemical additives. In this study, we analyzed hydraulic fracturing wastewater samples using ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) as a nontargeted technique to assign unambiguous molecular formulas to singly charged molecular ions. Halogenated molecular formulas were identified and confirmed using isotopic simulation and MS-MS fragmentation spectra. The abundance of halogenated organic compounds in flowback fluids rather than older wastewaters suggested that the observed molecular ions might have been related to hydraulic fracturing additives and related subsurface reactions, such as through the reaction of shale-extracted chloride, bromide, and iodide with strong oxidant additives (e.g., hypochlorite, persulfate, hydrogen peroxide) and subsequently with diverse dissolved organic matter. Some molecular ions matched the exact masses of known disinfection byproducts including diiodoacetic acid, dibromobenzoic acid, and diiodobenzoic acid. The identified halogenated organic compounds, particularly iodinated organic molecules, are absent from inland natural systems and these compounds could therefore play an important role as environmental tracers.


Potentially misleading extratemporal lobe lesions in patients with temporal lobe epilepsy.
From a series of 217 consecutive temporal resections for intractable epilepsy between 1993 and 2000, we identified all patients with large non-neoplastic extratemporal lesions. Only patients with known postsurgical outcomes with follow up for more than two years were included. Fifteen patients were identified. All patients had a history of medically refractory epilepsy with clinical and ictal evidence of mesial temporal seizure onset. Eleven patients had extratemporal lesions ipsilateral to the seizure focus, whereas four patients had the lesions contralateral to the seizure focus. Nine of the 15 patients had evidence of hippocampal atrophy on magnetic resonance imaging (MRI). Following temporal resection, nine of these patients (60%) became seizure free (Engel class 1A), two patients were free of disabling seizures only (Engel class 1B), and two patients had a few early seizures but then became seizure free for at least two years (Engel class 1C). Two patients had significant improvement (Engel class 2). Thus, the finding of large extratemporal lesions on MRI was potentially misleading. When clinical semiology and ictal EEG recordings provide evidence of temporal onset seizures, anterior temporal resection should be considered in patients with extratemporal lesions.


Cervical Spine Pathology Increases the Risk of Rotator Cuff Tear: A Population-Based Cohort Study.
Patients with cervical radiculopathy typically present with shoulder pain and weakness; these symptoms are similar to those of rotator cuff disease. Studies investigating cervical spine pathology (CSP) as an independent risk factor for rotator cuff tear (RCT) are lacking in the literature. To investigate the risk of RCT among patients with CSP who have undergone cervical diskectomy (CD) and to determine whether CD reduces this risk. Cohort study; Level of evidence, 3. The authors queried the Taiwan National Health Insurance Research Database for patients diagnosed with CSP between 2004 and 2008 and followed up until the end of 2010. A control cohort comprised patients without CSP who were age- and sex-matched in a 4-to-1 ratio with patients with CSP through propensity score matching. A Cox multivariate proportional hazards model was applied to analyze the risk factors for RCT. After adjustment for confounders, the authors calculated the hazard ratio (HR) and adjusted HR (aHR) between the study and control cohorts. The effects of CD on the risk of RCT were also analyzed. The study included 3245 patients and 12,980 matched controls. A higher RCT incidence rate was found in the CSP cohort, with an aHR of 1.52 (95% CI, 1.22-1.89; P < .001). Patients with CSP who underwent CD had a risk of RCT similar to that of the controls, with an aHR of 1.65 (95% CI, 0.90-3.03; P > .05). Patients with CSP had a 1.52-fold higher risk of RCT than healthy controls. Patients with CSP with CD did not have a high risk of RCT, possibly indicating a protective effect of diskectomy against RCT.


Immunotherapy of established murine B cell lymphoma. Combination of idiotype immunization and cyclophosphamide.
A murine B cell lymphoma (38C13) was used to study the efficacy of idiotype immunotherapy against established tumors. Immunization of mice with 38C13 tumor-derived Ig, administered after a lethal tumor inoculation, significantly prolonged survival of animals compared to control groups. The efficacy of active immunotherapy was dramatically enhanced when combined with chemotherapy. Cyclophosphamide (100 mg/kg), administered in combination with idiotype immunization to mice bearing 10-day-old, 1 to 2 cm diameter s.c. tumors, resulted in a significant prolongation of survival as compared with either cyclophosphamide or immunization alone and yielded approximately 50% cures. Additional studies combining active immunotherapy with surgical excision of the primary s.c. tumor nodule were less effective than combination chemoimmunotherapy, indicating that reduction of tumor burden was necessary, but not sufficient for effective treatment of established 38C13 lymphoma.


Indole Diterpene Derivatives from the Aspergillus flavus GZWMJZ-288, an Endophytic Fungus from Garcinia multiflora.
A new indole diterpene, 26-dihydroxyaflavininyl acetate (1), along with five known analogs (2-6) were isolated from the liquid fermentation of Aspergillus flavus GZWMJZ-288, an endophyte from Garcinia multiflora. The structures of these compounds were identified through NMR, MS, chemical reaction, and X-ray diffraction experiments. Enzyme inhibition activity screening found that compounds 1, 4, and 6 have a good binding affinity with NPC1L1, among which compound 6 exhibited a stronger binding ability than ezetimibe at a concentration of 10 µM. Moreover, compound 5 showed inhibitory activity against α-glucosidase with an IC50 value of 29.22 ± 0.83 µM, which is 13 times stronger than that of acarbose. The results suggest that these aflavinine analogs may serve as lead compounds for the development of drugs targeting NPC1L1 and α-glucosidase. The binding modes of the bioactive compounds with NPC1L1 and α-glucosidase were also performed through in silico docking studies.


Forces to pierce cuticle of tarsi and material properties determined by nanoindentation: The Achilles' heel of bed bugs.
The mechanical properties of bed bug (Cimex lectularius L.) tarsi and pretarsi were investigated in order to evaluate their vulnerability to piercing by plant trichomes (sharp microscopic hairs). Nanoindentation was used to measure the force required to insert a sharp probe into the cuticle of these different regions, as well as to determine creep and reduced elastic moduli for the cuticle. Scanning electron microscopy was used to visualize the indents that had been generated by nanoindentation. The force required to insert a cube corner nanoindenter probe into the cuticle was determined for a range of displacements (1 to 9 μm) and strain rates (0.003 to 0.5 s-1). Greater force was required to insert this sharp probe at greater depth or at faster strain rates. A specific region of the pretarsus (membrane with microtrichia) more frequently pierced by trichomes during bed bug locomotion required approximately 20-30% less force, exhibited more creep, and had a lower reduced elastic modulus for the first micron of indentation compared to the other regions; although this pattern was not consistent for greater displacements. These mechanical attributes, which will facilitate the initial stage of puncture in addition to the presence of natural infoldings in the cuticle of this area, may make that area of the pretarsus particularly vulnerable to piercing. This information will help inform development of physical methods for control of insect pests such as bed bugs.


Pedobacter psychrophilus sp. nov., isolated from fragmentary rock.
Strain P4487AT was isolated during investigation of cultivable bacterial populations of environmental materials sampled at James Ross Island, Antarctica. It revealed Gram-stain-negative short rod-shaped cells producing a pink pigment. Phylogenetic analysis based on 16S rRNA gene sequences allocated strain P4487AT to the genus Pedobacter but showed that the strain represents a distinct intrageneric phylogenetic lineage clearly separated from remaining Pedobacter species. Phylogenetically, strain P4487AT formed a common branch with the Pedobacter arcticus and Pedobacter lignilitoris cluster while the highest value of 94.4 % 16S rRNA gene sequence similarity suggested that Pedobacter lentus is the most closely related species. Biochemical and physiological test results enabled the differentiation of strain P4487AT from all phylogenetically closely related species. Chemotaxonomic analyses of strain P4487AT showed MK-7 as the respiratory menaquinone, sym-homospermidine as the major polyamine, phosphatidylethanolamine and two unidentified lipids as the major polar lipids, presence of sphingolipids, and C16 : 1ω7c/C16 : 1ω6c (summed feature 3), iso-C15 : 0 and iso-C17 : 0 3-OH as the major fatty acids, all of which corresponded with characteristics of the genus Pedobacter. The results showed that strain P4487AT represents a novel species within the genus Pedobacter, for which the name Pedobacter psychrophilus sp. nov. is proposed. The type strain is P4487AT (=CCM 8644T=LMG 29436T).


The design and baseline characteristics for the HOPE Consortium Trial to reduce pain and opioid use in hemodialysis.
The HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis (HOPE Trial) is a multicenter randomized trial addressing chronic pain among patients receiving maintenance hemodialysis for end-stage kidney disease. The trial uses a sequential, multiple assignment design with a randomized component for all participants (Phase 1) and a non-randomized component for a subset of participants (Phase 2). During Phase 1, participants are randomized to Pain Coping Skills Training (PCST), an intervention designed to increase self-efficacy for managing pain, or Usual Care. PCST consists of weekly, live, coach-led cognitive behavioral therapy sessions delivered by video- or tele-conferencing for 12 weeks followed by daily interactive voice response sessions delivered by telephone for an additional 12 weeks. At 24 weeks (Phase 2), participants in both the PCST and Usual Care groups taking prescription opioid medications at an average dose of ≥20 morphine milligram equivalents per day are offered buprenorphine, a partial opioid agonist with a more favorable safety profile than full-agonist opioids. All participants are followed for 36 weeks. The primary outcome is pain interference ascertained at 12 weeks for the primary analysis. Secondary outcomes include additional patient-reported measures and clinical outcomes including falls, hospitalizations, and death. Exploratory outcomes include acceptability, tolerability, and efficacy of buprenorphine. The enrollment target of 640 participants was met 27 months after trial initiation. The findings of the trial will inform the management of chronic pain, a common and challenging issue for patients treated with maintenance hemodialysis. NCT04571619.


TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial.
Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.


Blood hemoglobin A1c levels and amyotrophic lateral sclerosis survival.
There are inconsistences regarding the correlation between diabetes or fasting blood glucose concentrations and the risk and survival of amyotrophic lateral sclerosis (ALS) in the previous studies. Moreover, the association between hemoglobin A1c (HbA1c) levels, which reflect long-term glycemic status, and ALS survival was not examined. A prospective cohort study including 450 Chinese sporadic ALS patients (254 men and 196 women; mean age: 55.4 y). We identified 223 deaths during average 1.6 years of follow-up. We assessed levels of fasting HbA1c (primary exposure) and glucose (secondary exposure) via ion exchange high-performance liquid chromatography and hexokinase/glucose-6-pgosphate dehydrogenase methods, respectively. Multivariate Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ALS mortality across the exposures. Our results indicated that, higher levels of HbA1c, but not fasting blood glucose concentrations, were significantly associated with higher risks of mortality. The adjusted HR was 1.40 (95% confidence interval (95% CI): 1.02-1.99) for HbA1c of 5.7-6.4%, and 2.06 (95% CI: 1.07-3.96) for HbA1c ≥6.5%, relative to HbA1c <5.7% (P trend =0.01), after adjustment for age, smoking, obesity, disease severity, site of onset, lifestyle, and other potential confounders. The adjusted HR was 1.38 (95% CI: 0.81-2.35, P trend =0.13) for fasting glucose concentrations ≥7.0 mmol/L vs <5.6 mmol/L. We did not observe any significant interactions between HbA1c levels and age, sex, smoking, body mass index, rate of disease progression of ALS, and site of onset (P-interactions >0.05 for all). In this prospective study, we observed that individuals with higher HbA1c levels at the baseline had higher risk of mortality, which is independent of other known risk factors.


Prevention of steroid-induced osteonecrosis of femoral head in systemic lupus erythematosus by anti-coagulant.
Although osteonecrosis of femoral head (ONF) is one of the serious complications in systemic lupus erythematosus (SLE) associated with corticosteroid therapy, there has been few trials of prevention of ONF described. We aimed to prevent ONF in steroid-treated SLE patients using anticoagulant, warfarin, conducting a multicenter prospective study. Sixty newly diagnosed SLE patients requiring 40 mg/day or more prednisolone were alternately assigned to either of two groups; a warfarin group and a control one. Warfarin (1 to approximately 5 mg/day) was started together with the beginning of steroid therapy and continued at least for three months. Patients were observed for the development of silent ONF by magnetic resonance imaging (MRI) and symptomatic ONF by plain radiography for over five years. The warfarin group consisted of 31 patients (62 hips) and the control one 29 patients (58 hips). Silent ONF developed in 13 hips (21%) and 19 hips (33%) in the warfarin group and the control group, respectively (P = 0.13). On the other hand, warfarin tended to prevent symptomatic ONF; only three hips of 62 (4.8 %) in the warfarin group and eight hips of 58 (14%) in the control group (P = 0.08) developed silent ONF. It was also found that silent ONF developed, if it did, very early; within three months in 16 of 18 patients (89%). Among risk factors for silent ONF, steroid pulse therapy was most outstanding and it seemed to overcome the effect of warfarin. Taken together, for the time being, anti-coagulant therapy, if not significantly sufficient, may be of use for the prevention of steroid-induced ONF in SLE. We consider that this study added to important evidence for the pathogenesis and prevention of ONF.


Controlled gelation of poly(3-alkylthiophene)s in bulk and in thin-films using low volatility solvent/poor-solvent mixtures.
Low volatility solvent/non-solvent mixtures were utilized to engineer the structure of poly(3-alkylthiophene) (P3AT) organogels. The ratio of solvent to poor-solvent was manipulated to systematically control the kinetics of self-assembly. Specific solvent mixtures were utilized to produce similar gelation kinetics with polymers of differing alkyl chain length. Simultaneous small angle neutron scattering (SANS) and dielectric spectroscopy was used to probe the structure and the electronic properties of isothermally self-assembled P3ATs. It was determined that alkyl chain length has a dominant effect on the relationship between fiber development and conductivity. Furthermore, using transmission electron microscopy (TEM) and SANS we demonstrate that, for P3HT organogels, lower poor-solvent content leads to fewer fibers with larger nucleation centers while higher poor-solvent amounts results in more fibers and nucleation centers that are smaller and more abundant. This leads to opposing effects in terms of the contribution of the solvent quality to the electrical conductivity. An optimum in conductivity is found at different amounts of poor-solvent for each type of polymer. It is also shown that low volatility solvent mixtures allow for the formation of thermoreversible conjugated polymer organogels in thin-films at room temperature. This work highlights the potential to engineer the structure of conjugated polymer organogels while enabling the use of interconnected gel structures in thin-film organic electronic devices.


Vegetarian diets : nutritional considerations for athletes.
The quality of vegetarian diets to meet nutritional needs and support peak performance among athletes continues to be questioned. Appropriately planned vegetarian diets can provide sufficient energy and an appropriate range of carbohydrate, fat and protein intakes to support performance and health. The acceptable macronutrient distribution ranges for carbohydrate, fat and protein of 45-65%, 20-35% and 10-35%, respectively, are appropriate for vegetarian and non-vegetarian athletes alike, especially those who perform endurance events. Vegetarian athletes can meet their protein needs from predominantly or exclusively plant-based sources when a variety of these foods are consumed daily and energy intake is adequate. Muscle creatine stores are lower in vegetarians than non-vegetarians. Creatine supplementation provides ergogenic responses in both vegetarian and non-vegetarian athletes, with limited data supporting greater ergogenic effects on lean body mass accretion and work performance for vegetarians. The potential adverse effect of a vegetarian diet on iron status is based on the bioavailability of iron from plant foods rather than the amount of total iron present in the diet. Vegetarian and non-vegetarian athletes alike must consume sufficient iron to prevent deficiency, which will adversely affect performance. Other nutrients of concern for vegetarian athletes include zinc, vitamin B12 (cyanocobalamin), vitamin D (cholecalciferol) and calcium. The main sources of these nutrients are animal products; however, they can be found in many food sources suitable for vegetarians, including fortified soy milk and whole grain cereals. Vegetarians have higher antioxidant status for vitamin C (ascorbic acid), vitamin E (tocopherol), and beta-carotene than omnivores, which might help reduce exercise-induced oxidative stress. Research is needed comparing antioxidant defences in vegetarian and non-vegetarian athletes.


Rescue of DNA damage-stalled RNA Pol II: histone H2B in action.
RNA Pol II elongation in eukaryotes is coupled with a series of histone modifications. Elongating RNA Pol II can be strongly stalled by lesions on the DNA template. However, it is unclear whether RNA Pol II stalling affects elongation-associated histone modifications. We have explored this important question by investigating the function of histone H2B mono-ubiquitylation (H2Bub), a well-characterized epigenetic mark associated with RNA Pol II elongation, in the cellular response to DNA lesions induced by ultraviolet (UV) radiation. We found that, in contrast to transcription elongation, RNA Pol II stalling induced by UV lesions triggers rapid and significant H2B deubiquitylation that removes ubiquitin from H2B. Interestingly, in yeast mutant cells that lack H2B deubiquitylation enzymes, rescue of the stalled RNA Pol II by transcription-coupled repair (TCR) is significantly impaired. Thus, our study has established a direct connection between RNA Pol II stalling and a histone modification response.


Why Do White Americans Oppose Race-Targeted Policies? Clarifying the Impact of Symbolic Racism.
Measures of symbolic racism (SR) have often been used to tap racial prejudice toward Blacks. However, given the wording of questions used for this purpose, some of the apparent effects on attitudes toward policies to help Blacks may instead be due to political conservatism, attitudes toward government, and/or attitudes toward redistributive government policies in general. Using data from national probability sample surveys and an experiment, we explored whether SR has effects even when controlling for these potential confounds and whether its effects are specific to policies involving Blacks. Holding constant conservatism and attitudes toward limited government, SR predicted Whites' opposition to policies designed to help Blacks and more weakly predicted attitudes toward social programs whose beneficiaries were racially ambiguous. An experimental manipulation of policy beneficiaries revealed that SR predicted policy attitudes when Blacks were the beneficiary but not when women were. These findings are consistent with the claim that SR's association with racial policy preferences is not due to these confounds.


Household context and self-rated health: the effect of unemployment and informal work.
This article investigates whether the presence of residents in precarious work situations influences the self-rated health of people living in the same household. The study is based on the National Household Survey (PNAD) carried out in 1998 (n = 85,384) and 2003 (n = 89,063) by the Brazilian Institute of Geography and Statistics. These samples included all individuals aged 15 years and over, who lived in large metropolitan regions of Brazil. The effects at individual and household levels were estimated by the generalised estimation equations (GEE). At the individual level, poor self-rated health was inversely associated with schooling and positively associated with female sex, older age, informal work, unemployment and not economically active. Living in households with at least one informal or unemployed worker was positively associated with poor self-rated health, regardless of individual factors and socioeconomic characteristics of the household in 1998 (informal work: OR 1.09; 95% CI 1.06 to 1.12; unemployment: OR 1.08; 95% CI 1.04 to 1.13), and in 2003 (informal work: OR 1.06; 95% CI 1.03 to 1.10; unemployment: OR 1.10; 95% CI 1.05 to 1.15). These results suggest that unemployment and/or informal work have a contextual impact on the self-rated health of household dwellers. They add to the hypothesis that adverse conditions in the labour market and their impact on the health of individuals and groups are relevant in understanding inequalities in health.


[Diagnosis of pulmonary infections by specific etiologic agents in secondary immunocompromised patients].
Ten cases of pulmonary infections by the specific etiologic agents in immunocompromised patients secondary to diseases and/or drugs were reported. Their infections included 5 tuberculosis, 4 pulmonary aspergillosis, 1 Pneumocystis Carinii and cytomegalovirus pneumonia. The early revelation of pulmonary abnormality, the sampling of non-contaminated diagnostic materials, the improvement of laboratory techniques, and a feasible scheme of clinical management for pulmonary infections in immunocompromised patient were discussed.


In vitro to in vivo extrapolation of effective dosimetry in developmental toxicity testing: Application of a generic PBK modelling approach.
Incorporation of kinetics to quantitative in vitro to in vivo extrapolations (QIVIVE) is a key step for the realization of a non-animal testing paradigm, in the sphere of regulatory toxicology. The use of Physiologically-Based Kinetic (PBK) modelling for determining systemic doses of chemicals at the target site is accepted to be an indispensable element for such purposes. Nonetheless, PBK models are usually designed for a single or a group of compounds and are considered demanding, with respect to experimental data needed for model parameterization. Alternatively, we evaluate here the use of a more generic approach, i.e. the so-called IndusChemFate model, which is based on incorporated QSAR model parametrization. The model was used to simulate the in vivo kinetics of three diverse classes of developmental toxicants: triazoles, glycol ethers' alkoxyacetic acid metabolites and phthalate primary metabolites. The model required specific input per each class of compounds. These compounds were previously tested in three alternative assays: the whole-embryo culture (WEC), the zebrafish embryo test (ZET), and the mouse embryonic stem cell test (EST). Thereafter, the PBK-simulated blood levels at toxic in vivo doses were compared to the respective in vitro effective concentrations. Comparisons pertaining to relative potency and potency ranking with integration of kinetics were similar to previously obtained comparisons. Additionally, all three in vitro systems produced quite comparable results, and hence, a combination of alternative tests is still preferable for predicting the endpoint of developmental toxicity in vivo. This approach is put forward as biologically more plausible since plasma concentrations, rather than external administered doses, constitute the most direct in vivo dose metric.