Whole Blood Levels of the n-6 Essential Fatty Acid Linoleic Acid Are Inversely Associated with Stunting in 2-to-6 Year Old Tanzanian Children: A Cross-Sectional Study.
In Tanzania, 35% of all children below five years of age are stunted. Dietary fatty acids (FA) are critical for growth and development. However, whole blood FA levels in Tanzanian children are poorly described. The objectives of this cross-sectional study were to assess 1) whole blood levels of essential fatty acids and 2) the association between whole blood FA levels and growth parameters in Tanzanian children 2-6 years of age. A drop of blood was collected on an antioxidant treated card and analyzed for FA composition. Weight and height were measured and z-scores calculated. Relationships between FAs and growth parameters were analyzed by linear regression. Of the 334 children that participated, 30.3% were stunted. The average whole blood level of Mead acid was 0.15%. The anthropometric z-score height-for-age (HAZ) was inversely associated with Mead acid, the Mead acid to arachidonic acid (T/T) ratio, and total n-9 FA. Additionally, HAZ was positively associated with linoleic acid and total n-6 FA. BMI-for-age was positively associated with oleic acid, total n-9 FA and T/T ratio but inversely associated with arachidonic acid and total n-6 FA. Weight-for-height was inversely associated with arachidonic acid and total n-6 FAs and positively associated with oleic acid and total n-9 FA. Weight-for-age was not associated with any FA tested. Total n-3 FAs were not associated with any growth parameters measured. The EFA linoleic acid and the markers of FA deficiency were associated with HAZ, an indicator for stunting in 2-6 year old Tanzanian children. Total n-6, total n-9, and a number of individual FAs were associated with growth. Increasing dietary intake of EFA and n-6 FAs may be a strategy to combat stunting in this population.


The role of disease management in pay-for-performance programs for improving the care of chronically ill patients.
To date, pay-for-performance programs targeting the care of persons with chronic conditions have primarily been directed at physicians and provide an alternative to health plan-sponsored chronic disease management (DM) programs. Both approaches require similar infrastructure, and each has its own advantages and disadvantages for program implementation. Pay-for-performance programs use incentives based on patient outcomes; however, an alternative system might incorporate measures of structure and process. Using a conceptual framework, the authors explore the variation in 50 diabetes DM programs using data from the 2002 National Business Coalition on Health's eValue8 Request for Information (RFI). The authors raise issues relevant to the assignment of accountability for patient outcomes to either health plans or physicians. They analyze the association between RFI scores measuring structures and processes, and HEDIS diabetes intermediate outcome measures. Finally, the strengths and weaknesses of using the RFI scores as an alternative metric for pay-for-performance programs are discussed.


Person-centred reviews as a mechanism for planning the post-school transition of young people with intellectual disability.
Person-centred planning has played a key role in the transformation of intellectual disabilities services for more than a decade. The literature has identified clear advantages for service users when service delivery is planned around the individual rather than the user is made to fit into service structures. Researchers however have pointed out that there is a lack of evidence that person-centred planning positively influences outcomes for users. Our study examined the application of person-centred planning during transition for young people with intellectual disabilities. We investigated the nature and content of 44 person-centred reviews of transition planning for this population in a local authority in the UK. We carried out a documentary analysis of all person-centred plans and conducted telephone interviews with all families participating in the programme. We focused on the issue of attendance at review meetings and what was discussed during the meetings. Analysis of the data shows an increase in the participation of young people and carers at review meetings and a significant shift in topics discussed during the transition planning process compared with previous programmes. However, some of these effects may dissipate once young people are actually leaving school as planning well is not synonymous with having an improved range of placement options. The findings suggest that person-centred planning can impact positively on some aspects of transition planning, while it may be too optimistic to expect radical improvement in other area. Key to further improvements is to complement person-centred planning with consistent involvement of all relevant stakeholders in planning for individuals.


A survey of Nipah virus infection among various risk groups in Singapore.
Following the Nipah virus (NV) outbreak in March 1999 in Singapore, a serological survey was undertaken to screen individuals potentially exposed to NV. Blood samples were tested for NV IgM, IgG and neutralizing antibodies. Twenty-two (1.5%) of 1469 people tested had antibodies suggesting NV infection. Although 12 of the 22 infected people (54.6%) were symptomatic, the remaining 10 (45.4%) were clinically well and had no past history of compatible pulmonary or neurological disease. Clinical and serological findings suggested three people had been infected with NV before the outbreak was recognized. All those who were infected were male abattoir workers. None of the people who had contact with horses, and no healthcare workers exposed to infected patients and their specimens had detectable antibodies. This study provides evidence that NV causes asymptomatic infection. All of the antibody positive individuals had direct contact with pigs and there was no evidence of human to human transmission.


Physiological and pathological regulation of feto/placento/maternal leptin expression.
There is clear evidence of placental leptin production, as shown recently in trophoblast cultures and by dual in vitro placenta perfusion (median production of 225 pg/min per g of tissue; 98.4% released into the maternal and 1.6% into the fetal circulation). However, the physiological impact for the mother and the fetus is unclear. The classical role of leptin is to provide information about energy stores to the central nervous system, and to reduce appetite if the energy stores are full. In pregnancy, maternal plasma leptin concentrations are elevated, and lack the well established correlation with body fat energy stores that is observed in non-pregnant women, indicating an alternative function for leptin during pregnancy and fetal development. Maternal and fetal plasma leptin levels are dysregulated in pathological conditions such as gestational diabetes, pre-eclampsia and intra-uterine growth retardation, representing an effect or a cause of disturbances in the feto/placento/maternal unit.


Artemisinin derivatives versus quinine for cerebral malaria in African children: a systematic review.
To summarize the existing evidence on the efficacy of artemether and arteether, two artemisinin derivatives, versus quinine for treating cerebral malaria in children. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and the http://clinicaltrials.gov web site. We also checked the reference lists of existing systematic reviews and of all trials identified by the above methods. We searched exclusively for randomized controlled trials (RCTs) comparing artemether/arteether with quinine for treating cerebral malaria in children. Two independent reviewers assessed study eligibility and trial quality and extracted the data. Nine RCTs were included in the analysis, and all were from Africa. Five had adequate allocation concealment. Seven trials compared artemether with quinine (1220 children), and two compared arteether with quinine (194 children). No statistically significant difference was found between artemisinin derivatives and quinine in preventing mortality (relative risk, RR: 0.91; 95% confidence interval, CI: 0.73-1.14; I(2): 0%). The quality of the evidence, as assessed by the Grade evidence profile, was moderate. The only serious adverse event was seen in a patient in the quinine group who developed fatal black water fever. Artemisinin derivatives are not inferior to quinine in preventing death in children with cerebral malaria.


A case of macrocephaly-cutis marmorata telangiectatica congenita and review of neuroradiologic features.
Macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) is characterized by macrocephaly, cutis marmorata, capillary malformations, toe syndactily, joint laxity and pre-natal overgrowth. Cerebral abnormalities might also be seen. We reported cerebral magnetic resonance imaging (MRI) findings of a case with M-CMTC, who had giant atrial septal aneurysm and atrial septal defect. Cerebral alterations determined by MRI were bilateral prominent lateral ventricles, bilateral cortical dysplasia, cavum septi pellucidum cyst and calvarial hemangioma. At 17th day of his life he suddenly developed cardiorespiratory arrest and died.


Comparison of urinary monitoring, faecal monitoring and erythrocyte analysis of stable isotope labels to determine magnesium absorption in human subjects.
We have evaluated urinary monitoring and erythrocyte analysis to determine Mg absorption in human subjects as alternatives to the conventional technique of faecal monitoring by stable-isotope techniques. Ten healthy adults received 2.2 mmol (25)Mg in water, together with wheat bread, followed 15 min later by intravenous injection of 0.6 mmol (26)Mg (day 1). Brilliant blue and Yb (given on day 0 and day 1 respectively) served as qualitative and quantitative faecal markers. Urine was collected for 6 d after test meal intake. Complete collections of faeces were made until excretion of the second brilliant blue marker (given on day 7). Mg isotope ratios were determined by thermal ionisation-MS in urine and faeces and by inductively coupled plasma-MS in erythrocytes. Absorption was determined based on: (1) 6 d urine pools; (2) 24 h urine pools (collected 22-46 h after test meal intake); (3) erythrocytes from a blood sample drawn on day 14; (4) complete 6 d faecal pools; (5) faecal pools based on the first three consecutive stools after excretion of the first brilliant blue marker. Differences in mean Mg absorption (42 44 %) were statistically insignificant between techniques, except when based on 6 d urine pools for which the value was significantly lower (33 (sd 7) %, P=0.0003, ANOVA). The results indicate that Mg absorption can be determined from 24 h urine pools or erythrocytes obtained 14 d after test meal intake, an alternative method to the more time-consuming and labour-intense faecal monitoring. The choice of technique depends on practical and financial considerations.


Caloric intake and eating behavior in infants and toddlers with cystic fibrosis.
Infants and toddlers with cystic fibrosis (CF) are at risk for poor growth. Controlled behavioral assessment studies have not focused on this population. This study compared calorie intake, percentage of Recommended Daily Allowance (RDA) per day and per kilogram, and percentage of calories from fat, protein, and carbohydrates between infants and toddlers with CF and healthy peers. Also, eating behaviors, such as meal duration, bites and sips per minute, percentage of meal spent eating, children's problematic eating behaviors, and parents' perceptions of mealtime behaviors were compared between infants and toddlers with CF and controls. Five hypotheses were tested. 1) Infants and toddlers with CF would be comparable to controls on the number of calories consumed per day and the percentage of calories from fat. 2) Infants and toddlers with CF would not meet the CF dietary guidelines for the percentage of RDA for calories or the percentage of calories from fat. 3) Infants and toddlers with CF would have longer meal durations than healthy peers, but would not differ on the pace of eating, the number of calories consumed during the meal, or the percentage of time spent eating during the meal. 4) Parents of infants and toddlers with CF would perceive more problematic mealtime behavior than controls. 5) Parents' perceptions of children's mealtime behavior would positively correlate with meal duration and negatively correlate with the number of calories consumed during the meal. A 2-group comparison study. A clinical sample of 35 infants and toddlers with CF (M = 18.6; standard deviation = 8.1 months; range = 7-35 months) and a community sample of 34 healthy peers matched for age, gender, socioeconomic status, and number of parents and siblings present during mealtimes. Children's calorie intake was measured using 3-day diet diaries. The 2 groups did not differ on the total number of calories consumed per day, the percentage of calories derived from fat, or the percentage of RDA consumed per day. Infants and toddlers with CF were not meeting the CF dietary recommendations of 120% to 150% RDA for energy with 40% of calories coming from fat. Using the Dyadic Interaction Nomenclature for Eating, a behavioral coding system, videotaped recordings of children's dinner meals were scored for meal duration, number of bites and sips per minute, number of calories per bite or sip, and the percentage of 10-second intervals with bites and sips. The CF sample had significantly longer mealtimes (20.2 minutes) than the control group (16.4 minutes), but did not differ on calories consumed at the meal, bites and sips per minute, calories per bite and sip, or time spent eating during the meal. On the Behavioral Pediatrics Feeding Assessment Scale, a measure of parental perceptions of mealtime behavior that was completed by a subset of families (39 families), parents of infants and toddlers with CF endorsed a greater number of mealtime behaviors as problems and a higher occurrence of problems than did parents of controls. Examples of these behaviors for the CF sample included problems with their child's willingness to try new foods (48%), eat vegetables (48%), and observations that their child has a poor appetite (32%) and would rather drink than eat (32%). Parents of children with CF chose a greater number of mealtime strategies and feelings as problems and reported more frequently using problematic strategies at mealtimes than did parents of controls. Examples of problematic strategies and feelings for parents of infants and toddlers with CF included feeling anxious/frustrated when feeding their children (37%), not feeling confident that their child eats enough (32%), and using coaxing to get their child to take a bite (26%). For the entire sample, a positive correlation of 0.29 was found between the number of mealtime behavior problems reported by parents and meal duration, suggesting the co-occurrence of problematic mealtime behavior with longer meal duration. No relationship was found between the number of child mealtime behavior problems reported by parents and the number of calories consumed during the filmed meal. For the CF sample, a correlation of -0.26 between children's weight percentile for age and the filmed meal duration was found, suggesting a tendency for meal duration to increase as children's weight for age decreases. Post-hoc analyses were conducted comparing infants and toddlers with previously reported samples of preschool and school-aged children on meal duration. Results demonstrated that in each group, children with CF had longer meals than age-matched controls. Our findings reveal significant deficits in achieving dietary recommendations for many families of infants and toddlers with CF. Only 11% of infants and toddlers with CF met the CF dietary recommendation of at least 120% of the RDA/day for energy. In addition, infants and toddlers were found to derive only 34% of their daily calories from fat, compared with the recommended 40% needed for a moderate to high fat diet. These results underscore the need for intervention in families of infants and toddlers with CF, who in addition to being at increased risk for malnutrition, may also experience a hastening in the decline of their pulmonary status because of poor nutritional status. Currently, there is limited programmatic research on nutritional and feeding interventions for toddlers and infants with CF. One study, which used a hospital-based behavioral education program to increase the caloric intake of 3 children (ages 10-20 months) who were below the fifth percentile for weight for length, found at least a 54% increase in calories for each child after treatment. Similarly, preliminary findings of 2 parent-based interventions, a nutrition education curriculum and a nutrition education plus behavior parent-training curriculum, found a 22% and 32% increase in daily calories, respectively, at treatment completion. A large-scale clinical trial is needed to evaluate the efficacy of any nutritional intervention before widespread dissemination. Additional assessment-focused research is also needed to identify patients' who may be at greatest risk for malnutrition and to guide the development of interventions to treat them.


[Layout proposal for a microtitre plate to be used in routine antimicrobial susceptibility testing of bacteria from infections of dogs and cats].
The determination of minimum inhibitory concentrations by broth microdilution is recommended as method of choice for susceptibility testing of veterinary bacterial pathogens. Accordingly, broth microdilution is used in veterinary routine diagnostic laboratories at a progressive rate. To reduce the costs of susceptibility testing, it is reasonable to develop widely accepted uniform microtitre plate layouts that are produced in large quantities. Such microtitre plate layouts have already been developed and published for the susceptibility testing of pathogens from food-producing animals. However, a microtitre plate layout, especially designed for the testing of bacteria from dogs and cats, should be available, too. The choice of the antimicrobial agents or combinations of antimicrobial agents to be included in a suitable layout should be based on the following criteria: (1) the approval and availability of an antimicrobial agent or combination of agents, (2) known cross-resistances, and (3) availability of approved clinical breakpoints. The latter point is of particular importance for the choice of the numbers of concentrations per antimicrobial agent tested and the range of test concentrations. Taking into account these aspects, a science-based layout proposal for microtitre plates, which are suitable for routine testing of bacteria from dogs and cats, is presented and discussed.


Alpha-mangostin inhibits both dengue virus production and cytokine/chemokine expression.
Since severe dengue virus (DENV) infection in humans associates with both high viral load and massive cytokine production - referred to as "cytokine storm", an ideal drug for treatment of DENV infection should efficiently inhibit both virus production and cytokine expression. In searching for such an ideal drug, we discovered that α-mangostin (α-MG), a major bioactive compound purified from the pericarp of the mangosteen fruit (Garcinia mangostana Linn), which has been used in traditional medicine for several conditions including trauma, diarrhea, wound infection, pain, fever, and convulsion, inhibits both DENV production in cultured hepatocellular carcinoma HepG2 and Huh-7 cells, and cytokine/chemokine expression in HepG2 cells. α-MG could also efficiently inhibit all four serotypes of DENV. Treatment of DENV-infected cells with α-MG (20μM) significantly reduced the infection rates of four DENV serotypes by 47-55%. α-MG completely inhibited production of DENV-1 and DENV-3, and markedly reduced production of DENV-2 and DENV-4 by 100 folds. Furthermore, it could markedly reduce cytokine (IL-6 and TNF-α) and chemokine (RANTES, MIP-1β, and IP-10) transcription. These actions of α-MG are more potent than those of antiviral agent (ribavirin) and anti-inflammatory drug (dexamethasone). Thus, α-MG is potential to be further developed as therapeutic agent for DENV infection.


Regulatory NK cells suppress antigen-specific T cell responses.
The immune system has a variety of regulatory/suppressive processes, which are decisive for the development of a healthy or an allergic immune response to allergens. NK1 and NK2 subsets have been demonstrated to display counterregulatory and provocative roles in immune responses, similar to Th1 and Th2 cells. T regulatory cells suppressing both Th1 and Th2 responses have been the focus of intensive research during the last decade. In this study, we aimed to investigate regulatory NK cells in humans, by characterization of NK cell subsets according to their IL-10 secretion property. Freshly purified IL-10-secreting NK cells expressed up to 40-fold increase in IL-10, but not in the FoxP3 and TGF-beta mRNAs. PHA and IL-2 stimulation as well as vitamin D3/dexamethasone and anti-CD2/CD16 mAbs are demonstrated to induce IL-10 expression in NK cells. The effect of IL-10+ NK cells on Ag-specific T cell proliferation has been examined in bee venom major allergen, phospholipase A2- and purified protein derivative of Mycobecterium bovis-induced T cell proliferation. IL-10+ NK cells significantly suppressed both allergen/Ag-induced T cell proliferation and secretion of IL-13 and IFN-gamma, particularly due to secreted IL-10 as demonstrated by blocking of the IL-10 receptor. These results demonstrate that a distinct small fraction of NK cells display regulatory functions in humans.


Phase I Dose-Escalation and Pharmacokinetic Study of Intravenous Aflibercept in Combination with Docetaxel, Cisplatin, and 5-Fluorouracil in Patients with Advanced Solid Malignancies.
This phase I study (EudraCT No. 2006-001177-25) investigated aflibercept, a vascular endothelial growth factor decoy receptor protein (VEGF Trap), in combination with docetaxel, cisplatin, and 5-fluorouracil in patients with advanced solid tumors. Patients received 2, 4, or 6 mg/kg of intravenous aflibercept with docetaxel 75 mg/m2, cisplatin 75 mg/m2, and 5-fluorouracil 750 mg/m2 in 3-week cycles until disease progression or unacceptable toxicity. Primary objectives were to evaluate dose-limiting toxicities (DLTs) during cycle 1 and to determine the recommended phase II dose. Pharmacokinetics, tolerability, and antitumor activity were also investigated. Forty-four patients were enrolled and treated (29 patients in a dose-escalation phase and 15 patients in an expansion cohort). Following three cases of febrile neutropenia in patients receiving aflibercept at 4 mg/kg, the protocol was amended to allow earlier granulocyte colony-stimulating factor support (from day 6) and prophylactic use of ciprofloxacin. Subsequently, there were two DLTs: febrile neutropenia (2 mg/kg) and grade 4 pulmonary embolism (6 mg/kg). An excess of free over VEGF-bound aflibercept was observed at 6 mg/kg. The most frequent grade 3/4 adverse events (AEs) were neutropenia (54.5%), lymphopenia (47.7%), and stomatitis (38.6%). AEs associated with VEGF blockade (any grade) included epistaxis (61.4%), dysphonia (40.9%), hypertension (38.6%), and proteinuria (11.4%). There were 15 partial responses, including 9 in patients with gastroesophageal cancers. Thirteen patients had stable disease. Aflibercept 6 mg/kg administered every 3 weeks in combination with docetaxel, cisplatin, and 5- fluorouracil is the recommended dose for further clinical development based on tolerability, pharmacokinetics, and antitumor activity.


Nurses in Australian general practice: implications for chronic disease management.
The purpose of this study was to describe the demographic and employment characteristics of Australian practice nurses and explore the relationship between these characteristics and the nurses' role. Nursing in general practice is an integral component of primary care and chronic disease management in the United Kingdom and New Zealand, but in Australia it is an emerging specialty and there is limited data on the workforce and role. National postal survey embedded in a sequential mixed method design. 284 practice nurses completed a postal survey during 2003-2004. Descriptive statistics and factor analysis were utilized to analyse the data. Most participants were female (99%), Registered Nurses (86%), employed part-time in a group practice, with a mean age of 45.8 years, and had a hospital nursing certificate as their highest qualification (63%). The tasks currently undertaken by participants and those requiring further education were inversely related (R2 = -0.779). Conversely, tasks perceived to be appropriate for a practice nurse and those currently undertaken by participants were positively related (R2 = 0.8996). There was a mismatch between the number of participants who perceived that a particular task was appropriate and those who undertook the task. This disparity was not completely explained by demographic or employment characteristics. Extrinsic factors such as legal and funding issues, lack of space and general practitioner attitudes were identified as barriers to role expansion. Practice nurses are a clinically experienced workforce whose skills are not optimally harnessed to improve the care of the growing number of people with chronic and complex conditions. Relevance to clinical practice. Study data reveal a need to overcome the funding, regulatory and interprofessional barriers that currently constrain the practice nurse role. Expansion of the practice nurse role is clearly a useful adjunct to specialist management of chronic and complex disease, particularly within the context of contemporary policy initiatives.


Children's student nurses' knowledge of spirituality and its implications for educational practice.
Children's nurse educators have to rely predominantly on adult-based literature to guide their educational practice concerning spirituality in the nursing curriculum. The aim of this study was to get a children's nursing perspective. A questionnaire was designed around the main themes emerging from the adult literature on spirituality. This was distributed to children's nurses on the undergraduate curriculum at a UK university. The results showed that some of the challenges of delivering spirituality are common to both adult and children's nursing. However, there were also significant differences revolving around the impact that children and families had in informing students' understanding of spirituality, and the problems of seeking a unified theory of spirituality in a children's nursing context. It concludes that children's nursing has important lessons to learn from the adult literature; however, it must strive to construct its own insights and use this understanding to inform educational approaches to the topic.


Ontogeny of hyaluronan secretion during early mouse development.
The ontogeny of hyaluronan (HA) secretion during early mouse embryogenesis has been investigated using a biotin-labelled HA-binding complex from cartilage proteoglycan. HA is first secreted by visceral endoderm cells of the early egg cylinder on day 5.5 post coitum (p.c.), predominantly into the expanding yolk cavity. On day 6.5 p.c., HA is present in both the yolk and proamniotic cavities, but pericellular staining is restricted to the visceral endoderm and a population of embryonic ectoderm cells at the antimesometrial end of the proamniotic cavity. By the primitive streak stage, HA is secreted into the ectoplacental, exocoelomic, amniotic and yolk cavities, whilst the only cells exhibiting pericellular staining are those of the embryonic and extraembryonic mesoderm, including the allantois. Comparisons of HA-staining patterns of cultured whole blastocysts, microdissected trophectoderm fragments and immunosurgically isolated inner cell masses, revealed no trophoblast-associated HA secretion during outgrowth in vitro but significant synthetic activity by the endodermal derivatives of differentiating inner cell masses. To identify the cell lineages responsible for secretion of HA into the embryonic cavities and to investigate the origin of the HA observed around migrating mesoderm cells, day 7.5 p.c. primitive streak stage conceptuses were dissected into their various embryonic and extraembryonic cell lineages. HA secretion was observed after short-term suspension culture of mesoderm, embryonic ectoderm and embryonic endoderm, but was undetectable in fragments of ectoplacental cone, parietal yolk sac (primary giant trophoblast and parietal endoderm), extraembryonic ectoderm or extraembryonic endoderm. The level of synthesis by the HA-positive tissues was markedly enhanced by culture in medium containing serum, compared with that obtained following culture in medium supplemented with a defined serum substitute containing insulin, transferrin, selenous acid and linoleic acid. This suggests that additional growth factors, present in serum but absent from the serum substitute, are required for optimal HA synthesis by the HA-secreting tissues in vitro, and probably also in vivo. The implications of these events for implantation and the development of peri- and early post-implantation mouse embryos are discussed, and a new role for HA in the initial formation and expansion of the embryonic cavities is proposed.


Molecular events in B lymphocyte differentiation. Inducible expression of the endogenous mouse mammary tumor proviral gene, Mtv-9.
We have previously shown that the steady state levels of transcripts encoded by an endogenous mouse mammary tumor virus (MMTV) increase during LPS-induced differentiation of both normal B lymphocytes and an inducible B cell lymphoma, CH12. A large body of evidence suggests that MMTV expression is primarily limited to mammary tissues and that expression in cell lines from nonmammary tissues is accompanied by viral amplification and alterations in the transcriptional control regions of the viral long terminal repeat. We have, therefore, carefully characterized MMTV expression in CH12 cells and in other cells of the B lineage in order to determine if the expression of MMTV transcripts in differentiating B cells results from the "abnormal" transcriptional regulation seen in other nonmammary tissue. In this manuscript, we present evidence that MMTV transcripts are expressed in a variety of cells of the B lineage and that the levels of constitutive expression vary among the different cells. On the other hand, T cell lymphomas lacking amplified MMTV do not contain proviral transcripts, suggesting that MMTV transcription may be preferentially expressed in B lymphocytes. We demonstrate that MMTV transcripts are up-regulated during cytokine-mediated as well as LPS-mediated differentiation, and that most, if not all, expression is due to the activity of a single proviral gene, Mtv-9, in CH12 cells. Furthermore, the expression of MMTV transcripts in CH12 cells neither requires nor is accompanied by amplification of the provirus. Sequence analysis demonstrates that the U3 region of the expressed Mtv-9 long terminal repeat contains neither deletions nor insertions, and the well-characterized enhancer and promoter sites in the glucocorticoid response element which are known to be involved in transcriptional regulation of MMTV in mammary tissues have not been disrupted. These data suggest that the Mtv-9 locus behaves as a normal somatic gene which is differentially regulated during B cell development and differentiation. Unlike the events which lead to MMTV expression in other nonmammary tissues, B cells may express transcription factor(s) which are capable of inducing expression of endogenous MMTV proviral genes during the natural course of differentiation. Analysis of the mechanisms which control the expression of this gene should be useful in characterizing the molecular events which govern B cell differentiation.


Understanding palliative care on the heart failure care team: an innovative research methodology.
There is a growing call to integrate palliative care for patients with advanced heart failure (HF). However, the knowledge to inform integration efforts comes largely from interview and survey research with individual patients and providers. This work has been critically important in raising awareness of the need for integration, but it is insufficient to inform solutions that must be enacted not by isolated individuals but by complex care teams. Research methods are urgently required to support systematic exploration of the experiences of patients with HF, family caregivers, and health care providers as they interact as a care team. To design a research methodology that can support systematic exploration of the experiences of patients with HF, caregivers, and health care providers as they interact as a care team. This article describes in detail a methodology that we have piloted and are currently using in a multisite study of HF care teams. We describe three aspects of the methodology: the theoretical framework, an innovative sampling strategy, and an iterative system of data collection and analysis that incorporates four data sources and four analytical steps. We anticipate that this innovative methodology will support groundbreaking research in both HF care and other team settings in which palliative integration efforts are emerging for patients with advanced nonmalignant disease.


Capicua suppresses hepatocellular carcinoma progression by controlling the ETV4-MMP1 axis.
Hepatocellular carcinoma (HCC) is developed by multiple steps accompanying progressive alterations of gene expression, which leads to increased cell proliferation and malignancy. Although environmental factors and intracellular signaling pathways that are critical for HCC progression have been identified, gene expression changes and the related genetic factors contributing to HCC pathogenesis are still insufficiently understood. In this study, we identify a transcriptional repressor, Capicua (CIC), as a suppressor of HCC progression and a potential therapeutic target. Expression of CIC is posttranscriptionally reduced in HCC cells. CIC levels are correlated with survival rates in patients with HCC. CIC overexpression suppresses HCC cell proliferation and invasion, whereas loss of CIC exerts opposite effects in vivo as well as in vitro. Levels of polyoma enhancer activator 3 (PEA3) group genes, the best-known CIC target genes, are correlated with lethality in patients with HCC. Among the PEA3 group genes, ETS translocation variant 4 (ETV4) is the most significantly up-regulated in CIC-deficient HCC cells, consequently promoting HCC progression. Furthermore, it induces expression of matrix metalloproteinase 1 (MMP1), the MMP gene highly relevant to HCC progression, in HCC cells; and knockdown of MMP1 completely blocks the CIC deficiency-induced HCC cell proliferation and invasion. Our study demonstrates that the CIC-ETV4-MMP1 axis is a regulatory module controlling HCC progression. (Hepatology 2018;67:2287-2301).


Common mycorrhizal networks and their effect on the bargaining power of the fungal partner in the arbuscular mycorrhizal symbiosis.
Arbuscular mycorrhizal (AM) fungi form mutualistic interactions with the majority of land plants, including some of the most important crop species. The fungus takes up nutrients from the soil, and transfers these nutrients to the mycorrhizal interface in the root, where these nutrients are exchanged against carbon from the host. AM fungi form extensive hyphal networks in the soil and connect with their network multiple host plants. These common mycorrhizal networks (CMNs) play a critical role in the long-distance transport of nutrients through soil ecosystems and allow the exchange of signals between the interconnected plants. CMNs affect the survival, fitness, and competitiveness of the fungal and plant species that interact via these networks, but how the resource transport within these CMNs is controlled is largely unknown. We discuss the significance of CMNs for plant communities and for the bargaining power of the fungal partner in the AM symbiosis.


Doom, a product of the Drosophila mod(mdg4) gene, induces apoptosis and binds to baculovirus inhibitor-of-apoptosis proteins.
A family of baculovirus inhibitor-of-apoptosis (IAP) genes is present in mammals, insects, and baculoviruses, but the mechanism by which they block apoptosis is unknown. We have identified a protein encoded by the Drosophila mod(mdg4) gene which bound to the baculovirus IAPs. This protein induced rapid apoptosis in insect cells, and consequently we have named it Doom. Baculovirus IAPs and P35, an inhibitor of aspartate-specific cysteine proteases, blocked Doom-induced apoptosis. The carboxyl terminus encoded by the 3' exon of the doom cDNA, which distinguishes it from other mod(mdg4) cDNAs, was responsible for induction of apoptosis and engagement of the IAPs. Doom localized to the nucleus, while the IAPs localized to the cytoplasm, but when expressed together, Doom and the IAPs both localized in the nucleus. Thus, IAPs might block apoptosis by interacting with and modifying the behavior of Doom-like proteins that reside in cellular apoptotic pathways.


The effects of pressure on chondrocyte tumour necrosis factor receptor expression.
This work was performed to determine whether one aspect of load, pressure, could alter tumour necrosis factor (TNF) receptor type I (RI) expression on chondrocytes. Encapsulated tsT/AC62, osteoarthritic (OA) or non-arthritic (NA) chondrocytes were centrifuged at speeds representing 5 or 20 MPa, incubated for specific periods, released from alginate and TNFRI and II (TNFRII) expression determined by flow cytometry. Significant (p<0.05, n=4) changes in tsT/AC62 chondrocyte TNFRI expression were apparent 24 hours after application of 20 MPa. Five or 20 MPa increased OA chondrocyte TNFRI expression; chondrocytes from some OA patients were markedly sensitive to 20 MPa. NA chondrocyte TNFRI expression usually decreased in response to 5 and 20 MPa. Significant pressure-induced differences in TNFRI expression between NA and OA groups were apparent at 5, but not 20 MPa. Pressure did not significantly alter TNRFII expression on tsT/AC62, NA or OA chondrocytes. These results suggest a mechanism whereby sensitivity of chondrocytes to the effects of TNFalpha may be increased, in susceptible individuals, in regions of the joint that experience peak loading.


Photoprotective and immunoregulatory capacity of ginsenoside Rg1 in chronic ultraviolet B-irradiated BALB/c mouse skin.
The aim of this study was to investigate the photoprotective and immunoregulatory capacities of ginsenoside Rg1 in skin irradiated by chronic ultraviolet B (UVB) and to verify the potential mechanisms of action. BALB/c mice were pretreated with a topical application of ginsenoside Rg1 and irradiated with different doses of UVB daily for 30 consecutive days. Following chronic UVB irradiation, there were significant pathological changes in the skin of the BALB/c mice, including hyperkeratosis, acanthosis, sponge-like edematization and sunburn occurring in the epidermis, while edema, telangiectasis and inflammatory cell infiltration were observed in the papillary layer of the dermis. Treatment with ginsenoside Rg1 was able to reduce such changes induced by UVB irradiation. The number of p53 protein-positive stained cells following UVB irradiation was also observed by immunohistochemical analysis. Ginsenoside Rg1 downregulated the p53 protein expression induced by UVB irradiation, leading to reductions of 69.50, 23.53 and 12.93% at doses of 30, 60 and 120 mJ/cm2, respectively. Using reverse transcription polymerase chain reaction (RT-PCR), reductions in the levels of interferon (IFN)-γ mRNA expression were detected following UVB exposure; reductions of 19.6, 36.3 and 39.6% were observed following UVB irradiation at doses of 30, 60 and 120 mJ/cm2, respectively. The interleukin (IL)-10 mRNA expression levels increased by 40.1, 71.0 and 89.4% and the tumor necrosis factor (TNF)-α mRNA expression levels increased by 36.4, 18.4 and 8.6% following UVB irradiation at doses of 30, 60 and 120 mJ/cm2, respectively. However, pretreatment with ginsenoside Rg1 was observed to markedly attenuate the UVB irradiation-induced effects on the mRNA expression levels of the three cytokines. The topical application of ginsenoside Rg1 was able to protect the irradiated skin from UVB injury and reduce UVB-induced p53 protein expression. Ginsenoside Rg1 also demonstrated a potential regulatory effect on the UVB-induced local expression of the mRNA of the cytokines IFN-γ, IL-10 and TNF-α, which may be important in its immunoregulatory and inflammatory mechanisms.


Position of the American Dietetic Association, American Society for Nutrition, and Society for Nutrition Education: Food and nutrition programs for community-residing older adults.
Given the federal cost-containment policy to rebalance long-term care away from nursing homes to home- and community-based services, it is the position of the American Dietetic Association, the American Society for Nutrition, and the Society for Nutrition Education that all older adults should have access to food and nutrition programs that ensure the availability of safe, adequate food to promote optimal nutritional status. Appropriate food and nutrition programs include adequately funded food assistance and meal programs, nutrition education, screening, assessment, counseling, therapy, monitoring, evaluation, and outcomes documentation to ensure more healthful aging. The growing number of older adults, the health care focus on prevention, and the global economic situation accentuate the fundamental need for these programs. Yet far too often food and nutrition programs are disregarded or taken for granted. Growing older generally increases nutritional risk. Illnesses and chronic diseases; physical, cognitive, and social challenges; racial, ethnic, and linguistic differences; and low socioeconomic status can further complicate a situation. The beneficial effects of nutrition for health promotion, risk reduction, and disease management need emphasis. Although many older adults are enjoying longer and more healthful lives in their own homes, others, especially those with health disparities and poor nutritional status, would benefit from greater access to food and nutrition programs and services. Food and nutrition practitioners can play a major role in promoting universal access and integrating food and nutrition programs and nutrition services into home- and community-based services.


Risk assessment and risk-based programs of prevention in various settings.
An assortment of screening tools exist to estimate risk for pressure ulcer development. The Braden Scale has undergone testing in several settings which guide users in answering the following questions: Who should assess risk? Does cut-off score differ by setting? Does timing of assessment vary by setting? Is formal risk assessment necessary? How does risk assessment fit into a program of prevention? Based on these studies, RNs are able to use the Braden Scale more reliably than Nurse Aides and LPNs. While the Braden Scale does not replace clinical judgement, its use will help caregivers of all levels to identify at risk patients and intervene for specific risk factors. Generally, all patients should be assessed upon admission and 24 to 48 hours later, followed by ongoing assessment. A formal risk-based program is effective in both reducing the incidence of pressure ulcers and the costs associated with prevention. Protocols can be developed to address each level of risk, with each level requiring more aggressive preventive modalities. Some investigators have also tied interventions to specific subscale scores. It is important that risk assessment and risk-based protocols such as the Braden Scale become a standard of practice in all healthcare settings.


Atmospheric Sampling on Ascension Island Using Multirotor UAVs.
As part of an NERC-funded project investigating the southern methane anomaly, a team drawn from the Universities of Bristol, Birmingham and Royal Holloway flew small unmanned multirotors from Ascension Island for the purposes of atmospheric sampling. The objective of these flights was to collect air samples from below, within and above a persistent atmospheric feature, the Trade Wind Inversion, in order to characterise methane concentrations and their isotopic composition. These parameters allow the methane in the different air masses to be tied to different source locations, which can be further analysed using back trajectory atmospheric computer modelling. This paper describes the campaigns as a whole including the design of the bespoke eight rotor aircraft and the operational requirements that were needed in order to collect targeted multiple air samples up to 2.5 km above the ground level in under 20 min of flight time. Key features of the system described include real-time feedback of temperature and humidity, as well as system health data. This enabled detailed targeting of the air sampling design to be realised and planned during the flight mission on the downward leg, a capability that is invaluable in the presence of uncertainty in the pre-flight meteorological data. Environmental considerations are also outlined together with the flight plans that were created in order to rapidly fly vertical transects of the atmosphere whilst encountering changing wind conditions. Two sampling campaigns were carried out in September 2014 and July 2015 with over one hundred high altitude sampling missions. Lessons learned are given throughout, including those associated with operating in the testing environment encountered on Ascension Island.


Vapour permeation measurements with free-standing nanomembranes.
Mass transfer across porous materials with nanoscale thickness is of great interest in terms of both fundamentals of fluid dynamics and practical challenges of membrane separation. In particular, few-atom thick sieves are viewed as attractive candidates to achieve ultimate permeability without compromising membrane selectivity. In this work, we introduce a vacuum system for studying vapour and gas permeation in micrometre-sized samples of suspended nanometre-thick films. Steady-state permeation rates are measured with a mass-spectrometer directly connected to the downstream side of a membrane cell. A built-in nanoaperture is used as a reference to calibrate the detector in situ. A feed compartment is designed in a way that allows for preparing gaseous mixtures of variable composition, including vapours of volatile liquids. Room-temperature measurements with carbon nanomembranes confirm that this material is selective to water vapour and can efficiently separate it from mixtures with a variety of gases and organic compounds. We demonstrate that a high permeance for water is maintained regardless of the molar fraction and discuss its strong pressure dependence by invoking adsorption-related formalism.


Optimisation of imaging flow cytometry for the analysis of single extracellular vesicles by using fluorescence-tagged vesicles as biological reference material.
Extracellular vesicles (EVs) mediate targeted cellular interactions in normal and pathophysiological conditions and are increasingly recognised as potential biomarkers, therapeutic agents and drug delivery vehicles. Based on their size and biogenesis, EVs are classified as exosomes, microvesicles and apoptotic bodies. Due to overlapping size ranges and the lack of specific markers, these classes cannot yet be distinguished experimentally. Currently, it is a major challenge in the field to define robust and sensitive technological platforms being suitable to resolve EV heterogeneity, especially for small EVs (sEVs) with diameters below 200 nm, i.e. smaller microvesicles and exosomes. Most conventional flow cytometers are not suitable for the detection of particles being smaller than 300 nm, and the poor availability of defined reference materials hampers the validation of sEV analysis protocols. Following initial reports that imaging flow cytometry (IFCM) can be used for the characterisation of larger EVs, we aimed to investigate its usability for the characterisation of sEVs. This study set out to identify optimal sample preparation and instrument settings that would demonstrate the utility of this technology for the detection of single sEVs. By using CD63eGFP-labelled sEVs as a biological reference material, we were able to define and optimise IFCM acquisition and analysis parameters on an Amnis ImageStreamX MkII instrument for the detection of single sEVs. In addition, using antibody-labelling approaches, we show that IFCM facilitates robust detection of different EV and sEV subpopulations in isolated EVs, as well as unprocessed EV-containing samples. Our results indicate that fluorescently labelled sEVs as biological reference material are highly useful for the optimisation of fluorescence-based methods for sEV analysis. Finally, we propose that IFCM will help to significantly increase our ability to assess EV heterogeneity in a rigorous and reproducible manner, and facilitate the identification of specific subsets of sEVs as useful biomarkers in various diseases.


Role of topical emollients and moisturizers in the treatment of dry skin barrier disorders.
Emollients and moisturizing creams are used to break the dry skin cycle and to maintain the smoothness of the skin. The term 'moisturizer' is often used synonymously with emollient, but moisturizers often contain humectants in order to hydrate the stratum corneum. Dryness is frequently linked to an impaired barrier function observed, for example, in atopic skin, psoriasis, ichthyosis, and contact dermatitis. Dryness and skin barrier disorders are not a single entity, but are characterized by differences in chemistry and morphology in the epidermis. Large differences also exist between moisturizing creams. Moisturizers have multiple functions apart from moistening the skin. Similar to other actives, the efficacy is likely to depend on the dosage, where compliance is a great challenge faced in the management of skin diseases. Strong odor from ingredients and greasy compositions may be disagreeable to the patients. Furthermore, low pH and sensory reactions, from lactic acid and urea for example, may reduce patient acceptance. Once applied to the skin, the ingredients can stay on the surface, be absorbed into the skin, be metabolized, or disappear from the surface by evaporation, sloughing off, or by contact with other materials. In addition to substances considered as actives, e.g. fats and humectants, moisturizers contain substances conventionally considered as excipients (e.g. emulsifiers, antioxidants, preservatives). Recent findings indicate that actives and excipients may have more pronounced effects in the skin than previously considered. Some formulations may deteriorate the skin condition, whereas others improve the clinical appearance and skin barrier function. For example, emulsifiers may weaken the barrier. On the other hand, petrolatum has an immediate barrier-repairing effect in delipidized stratum corneum. Moreover, one ceramide-dominant lipid mixture improved atopic dermatitis and decreased transepidermal water loss (TEWL) in an open-label study in children. In double-blind studies moisturizers with urea have been shown to reduce TEWL in atopic and ichthyotic patients. Urea also makes normal and atopic skin less susceptible against irritation to sodium laurilsulfate. Treatments improving the barrier function may reduce the likelihood of further aggravation of the disease. In order to have optimum effect it is conceivable that moisturizers should be tailored with respect to the epidermal abnormality. New biochemical approaches and non-invasive instruments will increase our understanding of skin barrier disorders and facilitate optimum treatments. The chemistry and function of dry skin and moisturizers is a challenging subject for the practicing dermatologist, as well as for the chemist developing these agents in the pharmaceutical/cosmetic industry.


Examining the contribution of social communication abilities and affective/behavioral functioning to social integration outcomes for adults with traumatic brain injury.
To evaluate the contribution of social communication abilities and affective/behavioral functioning to social integration outcomes for persons with traumatic brain injury (TBI). Prospective cohort study. A total of 184 adults with TBI (72.8% men) evaluated at least 6 months postdischarge from acute care or inpatient rehabilitation hospitals and after living at least 3 months in the community postdischarge (Mean = 7.84 months postinjury). La Trobe Communication Questionnaire (LCQ), Assessment of Interpersonal Problem-Solving Skills(AIPSS), Affective Behavioral subscale From the Problem Checklist of the Head Injury Family Interview (AB-HIFI), Craig Handicap Assessment and Reporting Technique-Short Form Social Integration subscale (CHART-SF-SI), Community Integration Questionnaire Social Integration subscale (CIQ-SI). Social communication measures (LCQ, AIPSS) and self-reported behavioral functioning (AB-HIFI) contributed significantly to concurrently measured social integration outcomes after controlling for demographic and injury-related variables. Separate hierarchical multiple regression analyses revealed that social communication and behavioral variables accounted for 11.3% of variance in CIQ-SI and 16.3% of variance in CHART-SF-SI. Social communication abilities and affective/behavioral functioning make a substantial contribution to social integration outcomes after TBI. The implications of such evidence for clinical assessment and intervention are discussed.


Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation.
Human pluripotent stem cells have the capacity for directed differentiation into a wide variety of neuronal subtypes that may be useful for brain repair. While a substantial body of research has lead to a detailed understanding of the ability of neurons in fetal tissue grafts to structurally and functionally integrate after intra-cerebral transplantation, we are only just beginning to understand the in vivo properties of neurons derived from human pluripotent stem cells. Here we have utilized the human embryonic stem (ES) cell line Envy, which constitutively expresses green fluorescent protein (GFP), in order to study the in vivo properties of neurons derived from human ES cells. Rapid and efficient neural induction, followed by differentiation as neurospheres resulted in a GFP+ neural precursor population with traits of neuroepithelial and dorsal forebrain identity. Ten weeks after transplantation into neonatal rats, GFP+ fiber patterns revealed extensive axonal growth in the host brain, particularly along host white matter tracts, although innervation of adjacent nuclei was limited. The grafts were composed of a mix of neural cell types including differentiated neurons and glia, but also dividing neural progenitors and migrating neuroblasts, indicating an incomplete state of maturation at 10 weeks. This was reflected in patch-clamp recordings showing stereotypical properties appropriate for mature functional neurons, including the ability to generate action potentials, as well profiles consistent for more immature neurons. These findings illustrate the intrinsic capacity for neurons derived from human ES cells to integrate at a structural and functional level following transplantation.


Older patients' experiences during care transition.
A fragmented health care system leads to an increased demand for continuity of care across health care levels. Research indicates age-related differences during care transition, with the oldest patients having experiences and needs that differ from those of other patients. To meet the older patients' needs and preferences during care transition, professionals must understand their experiences. The purpose of the study was to explore how patients ≥80 years of age experienced the care transition from hospital to municipal health care services. The study has a descriptive, explorative design, using semistructured interviews. Fourteen patients aged ≥80 participated in the study. Qualitative content analysis was used to describe the individuals' experiences during care transition. Two complementary themes emerged during the analysis: "Participation depends on being invited to plan the care transition" and "Managing continuity of care represents a complex and challenging process". Lack of participation, insufficient information, and vague responsibilities among staff during care transition seemed to limit the continuity of care. The patients are the vulnerable part of the care transition process, although they possess important resources, which illustrate the importance of making their voice heard. Older patients are therefore likely to benefit from more intensive support. A tailored, patient-centered follow-up of each patient is suggested to ensure that patient preferences and continuity of care to adhere to the new situation.


Mitochondrial stress and redox failure in steroid-associated osteonecrosis.
The purpose of the role of antioxidant enzymes and mitochondria in the developmental mechanism of steroid-associated osteonecrosis in the femur. In the present study Japanese white rabbits (mean weight 3.5kg) were injected into the gluteus with methylprednisolone (MP) 20mg/kg, and killed after 3 days (MP3 group), 5 days (MP5 group), and 14 days (MP14 group) (n=3 each). As a Control group (C group) Japanese white rabbits not administered MP were used. In experiment 1, the expression of the antioxidant enzymes Superoxide dismutade (SOD) and catalase was compared in liver, kidney, heart, humerus, and femur in C group, and the presence/absence of mitochondria transcription factor A (TFAM) expression was determined by Western blotting (WB) and used to evaluate the number of mitochondria and their function. In experiment 2, the presence/absence of necrosis was determined by immunohistochemistry, while changes in the expression of SOD, catalase, and TFAM in the femur after steroid administration were determined by Western blotting (WB). In experiment 1, intense expression of all of SOD, catalase, and TFAM was found in the liver, kidney, and heart as compared to the humerus and femur. In experiment 2, the expression of all of SOD, catalase, and TFAM in MP3 and MP5 groups was decreased on WB as compared with C group, while in MP14 group a tendency to improvement was seen. Accordingly, steroid-associated mitochondrial injury and redox failure are concluded to be important elements implicated in the pathogenesis of osteonecrosis.


Applying evidence-based methods to the development and use of adverse outcome pathways
The workshop "Application of evidence-based methods to construct mechanistic frameworks for the development and use of non-animal toxicity tests" was organized by the Evidence-based Toxicology Collaboration and hosted by the Grading of Recommendations Assessment, Development and Evaluation Working Group on June 12, 2019. The purpose of the workshop was to bring together international regulatory bodies, risk assessors, academic scientists, and industry to explore how systematic review methods and the adverse outcome pathway framework could be combined to develop and use mechanistic test methods for predicting the toxicity of chemical substances in an evidence-based manner. The meeting covered the history of biological frameworks, the way adverse outcome pathways are currently developed, the basic principles of systematic methodology, including systematic reviews and evidence maps, and assessment of certainty in models, and adverse outcome pathways in particular. Specific topics were discussed via case studies in small break-out groups. The group concluded that adverse outcome pathways provide an important framework to support mechanism-based assessment in environmental health. The process of their development has a few challenges that could be addressed with systematic methods and automation tools. Addressing these challenges will increase the transparency of the evidence behind adverse outcome pathways and the consistency with which they are defined; this in turn will increase their value for supporting public health decisions. It was suggested to explore the details of applying systematic methods to adverse outcome pathway development in a series of case studies and workshops.


Identification of Metabolites and Transcripts Involved in Salt Stress and Recovery in Peanut.
HIGHLIGHTS Metabolites and transcripts related to plant physiology in salt stress conditions, especially to the recovery process were disclosed in peanut. Peanut (Arachis hypogaea L.) is considered as a moderately salt-sensitive species and thus soil salinity can be a limiting factor for peanut cultivation. To gain insights into peanut plant physiology in response to salt stress and alleviation, we comprehensively characterized leaf relative electrolyte leakage (REC), photosynthesis, leaf transpiration, and metabolism of plants under salt stress and plants that were subjected to salt stress followed by salt alleviation period. As expected, we found that REC levels were higher when plants were subjected to salt stress compared with the untreated plants. However, in contrast to expectations, REC was even higher compared with salt treated plants when plants were transferred from salt stress to standard conditions. To decipher REC variation in response to salt stress, especial during the recovery, metabolite, and transcript variations were analyzed by GC/MS and RNA-seq method, respectively. Ninety two metabolites, among total 391 metabolites identified, varied in response to salt and 42 metabolites responded to recovery specially. Transcriptomics data showed 1,742 in shoots and 3,281 in roots transcript varied in response to salt stress and 372 in shoots and 1,386 transcripts in roots responded specifically to recovery, but not salt stress. Finally, 95 transcripts and 1 metabolite are indicated as candidates involved in REC, photosynthesis, transpiration, and Na+ accumulation variation were revealed by using the principal component analysis (PCA) and correlation analysis. This study provides valuable information on peanut response to salt stress and recovery and may inspire further study to improve salt tolerance in peanut germplasm innovation.


Cell-Free DNA to Detect Heart Allograft Acute Rejection.
After heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker-percent donor-derived cell-free DNA (%ddcfDNA)-for detection of AR in cardiac transplant recipients. This multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis. The study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1-23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%-0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31-0.83%], versus 0.03% [IQR, 0.01-0.14%]; P<0.001). The rise was detected 0.5 and 3.2 months before histopathologic diagnosis of ACR and AMR. The area under the receiver operator characteristic curve for AR was 0.92. A 0.25%ddcfDNA threshold had a negative predictive value for AR of 99% and would have safely eliminated 81% of EMBx. In addition, %ddcfDNA showed distinctive characteristics comparing AMR with ACR, including 5-fold higher levels (AMR ≥2, 1.68% [IQR, 0.49-2.79%] versus ACR grade ≥2R, 0.34% [IQR, 0.28-0.72%]), higher area under the receiver operator characteristic curve (0.95 versus 0.85), higher guanosine-cytosine content, and higher percentage of short ddcfDNA fragments. We found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.


Comparative effectiveness of conservative and pharmacological interventions for chronic non-specific neck pain: Protocol of a systematic review and network meta-analysis.
Neck Pain (NP) has been ranked as one of the top chronic pain conditions in terms of prevalence and years lived with disability in the latest Global Burden of Disease. NP has remarkable socio-economic consequences however, research efforts are limited. Discrepancies among guidelines recommendations on management of chronic neck pain exist. The purpose of this study protocol is to provide the methods for a review with network meta-analysis to identify the most effective interventions for chronic neck pain. The following databases will be searched from their inception to February 2019: Cochrane Controlled Trials Register (CENTRAL), PubMed, CINAHL, Scopus, ISI Web of Science and PEDro.Randomized controlled trials (RCTs) on pharmacological and not pharmacological interventions will be included and their risk of bias will be evaluated using the Cochrane Risk of bias tool. Primary outcomes will be reduction in pain and disability. A network meta-analysis will be carried out and pairwise meta-analysis will be conducted using Stata 15 software. Grading of recommendations assessment, development, and evaluation (GRADE) will be applied to assess quality of the body of the evidence. The results of this review will be submitted to a peer-review journal for publication. This network meta-analysis will provide a comprehensive review on the most effective treatments for the management of chronic neck pain providing key evidence-based information to patients, clinicians and other relevant stakeholders. Registration: PROSPERO (registration number CRD42019124501).


Serum hemoglobin level determined at the first presentation is a poor prognostic indicator in patients with lung cancer.
Anemia is observed in various malignancies including lung cancer and is recently considered to be a poor prognostic indicator. We investigated whether there is a correlation between anemia, other clinicopathologic factors, and survival. We retrospectively examined the clinical records of 611 patients with lung cancer. Of those, 298 (48.8%) patients had anemia at the time of their first visit to our hospital. There was a significant correlation between anemia and age (p=0.0006) or ECOG performance status (p=0.0002), however, there was no correlation of anemia with gender, histological type, clinical stage, or serum level of lactate dehydrogenase. Survival was significantly shorter in 298 patients with anemia (median survival time (MST): 7.5 months) compared with 313 patients without anemia (MST: 11.8 months, p<0.0001). Multivariate analysis of prognostic factors using the Cox proportional hazards model revealed that anemia appeared to be an independent prognostic indicator. Anemia observed at the first presentation is an independent poor prognostic indicator in patients with lung cancer.


Leg extensor power and functional performance in very old men and women.
1. Residents of a chronic care hospital (13 men of mean age 88.5 +/- 6 SD years and 13 women of mean age 86.5 +/- 6 SD years) who had multiple pathologies were assessed for leg extensor capability in several ways. 2. A custom-built rig was used to assess leg extensor power, that is, maximal power output over less than 1 s in a single extension of one leg. Performance measures were obtained by timing chair rises (from a standard chair 0.43 m high), stair climbing (four risers, total height 0.635 m) and a walk (6.1 m). For each measurement the best of several trials were recorded as definitive. 3. Leg extensor power was significantly correlated with all performance measures, but the performance measures were not related to each other except for chair rising and walking speed. 4. Women had significantly less extensor power than men, but their power explained more of the variance in performance, e.g. power accounted for 86% of the variance in walking speed. 5. There was no relation within the group between age and any of the variables measured. 6. Measurement of leg extensor power in frail elderly people may prove useful in focusing effective rehabilitation programmes.


Crystal structures and DFT calculations of new chlorido-dimethylsulfoxide-M(III) (M = Ir, Ru, Rh) complexes with the N-pyrazolyl pyrimidine donor ligand: kinetic vs. thermodynamic isomers.
New chlorido-dimethylsulfoxide-iridium(III), ruthenium(III) and rhodium(III) complexes with the 2-(1H-pyrazol-1-yl)-pyrimidine (pyrapyr) ligand (OC-6-N1)-[Rh(III)Cl3(DMSO-κS)(pyrapyr)] (1a, N = 3 and 1b, N = 4); (OC-6-N1)-[Ru(III)Cl3(DMSO-κS)(pyrapyr)] (2a, N = 3 and 2b, N = 4) and (OC-6-N1)-[Ir(III)Cl3(DMSO-κS)(pyrapyr)] (3a, N = 3 and 3b, N = 4) have been synthesized and characterized by spectroscopic techniques and by single crystal X-ray diffraction studies (1a, 1b, 2a, 2b, a disordered crystal 3a/3b and a cocrystal 3a·3b). In all cases, the metal centers show octahedral geometry coordinated to three chloride ligands and one S coordinated dimethylsulfoxide (DMSO-κS). The coordination sphere of the metal is completed by the pyrapyr molecule. Two different coordination modes are observed: (i) the DMSO-κS is opposite to the pyrimidinic N atom (IUPAC nomenclature is OC-6-31 denoted herein as trans); (ii) DMSO-κS is opposite to the pyrazolic N atom (IUPAC nomenclature is OC-6-41 denoted as cis). For Rh(III) the kinetic product (cis) yields the thermodynamic (trans) upon heating a solution of the kinetic product and both isomers have been X-ray characterized. Conversely for Ru(III), both kinetic and thermodynamic complexes have been obtained by using different procedures. Both isomers have been characterized by X-ray crystallography and the kinetic product does not yield the thermodynamic upon heating a solution of the former. Furthermore, the Ir(III) behaves differently, since both isomers are energetically equivalent and both isomers co-crystallize in the solid state. The kinetic/thermodynamic mechanism that yields the different isomers has been studied by using theoretical DFT calculations for each metal. Finally, two Ru(II) complexes (OC-6-N1)-[Ru(II)Cl2(DMSO-κS)2(pyrapyr)] (1a, N = 3 and 4b, N = 4) are also described and X-ray characterized. They were obtained as minor products during the synthesis of 2a.


6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA) transport altered by two missense mutations in the drug transporter gene ABCC4.
Multiple drug resistance protein 4 (MRP4, ABCC4) belongs to the C subfamily of the ATP-binding cassette (ABC) transporter superfamily and participates in the transport of diverse antiviral and chemotherapeutic agents such as 6-mercaptopurine (6-MP) and 9-(2-phosphonyl methoxyethyl) adenine (PMEA). We have undertaken a comprehensive functional characterization of protein variants of MRP4 found in Caucasians and other ethnicities. A total of 11 MRP4 missense genetic variants (nonsynonymous SNPs), fused to green fluorescent protein (GFP), were examined in Xenopus laevis oocytes for their effect on expression, localization, and function of the transporter. Radiolabeled 6-MP and PMEA were chosen as transport substrates. All MRP4 protein variants were found to be expressed predominantly in the oocyte membrane. A total of four variants (Y556C, E757 K, V776I, and T1142 M) exhibited a 20% to 40% reduced expression level compared to the wild type. Efflux studies showed that 6-MP is transported by MRP4 in unmodified form. Compared to wild-type MRP4, the transmembrane variant V776I, revealed a significant lower activity in 6-MP transport, while the amino acid exchange Y556C in the Walker(B) motif displayed significantly higher transport of PMEA. The transport properties of the other variants were comparable to wild-type MRP4. Our study shows that Xenopus oocytes are well suited to characterize MRP4 and its protein variants. Carriers of the rare MRP4 variants Y556C and V776I may have altered disposition of MRP4 substrates.


An unusually powerful mode of low-frequency sound interference due to defective hair bundles of the auditory outer hair cells.
A detrimental perceptive consequence of damaged auditory sensory hair cells consists in a pronounced masking effect exerted by low-frequency sounds, thought to occur when auditory threshold elevation substantially exceeds 40 dB. Here, we identified the submembrane scaffold protein Nherf1 as a hair-bundle component of the differentiating outer hair cells (OHCs). Nherf1(-/-) mice displayed OHC hair-bundle shape anomalies in the mid and basal cochlea, normally tuned to mid- and high-frequency tones, and mild (22-35 dB) hearing-threshold elevations restricted to midhigh sound frequencies. This mild decrease in hearing sensitivity was, however, discordant with almost nonresponding OHCs at the cochlear base as assessed by distortion-product otoacoustic emissions and cochlear microphonic potentials. Moreover, unlike wild-type mice, responses of Nherf1(-/-) mice to high-frequency (20-40 kHz) test tones were not masked by tones of neighboring frequencies. Instead, efficient maskers were characterized by their frequencies up to two octaves below the probe-tone frequency, unusually low intensities up to 25 dB below probe-tone level, and growth-of-masker slope (2.2 dB/dB) reflecting their compressive amplification. Together, these properties do not fit the current acknowledged features of a hypersensitivity of the basal cochlea to lower frequencies, but rather suggest a previously unidentified mechanism. Low-frequency maskers, we propose, may interact within the unaffected cochlear apical region with midhigh frequency sounds propagated there via a mode possibly using the persistent contact of misshaped OHC hair bundles with the tectorial membrane. Our findings thus reveal a source of misleading interpretations of hearing thresholds and of hypervulnerability to low-frequency sound interference.


Surfing the data tsunami, a bioinformatic dissection of the proangiogenic monocyte.
In this review we compare expression studies on monocyte subsets as an example to show the integrated possibilities of molecular databases and bioinformatic analysis tools. Monocytes have been recognized as cells with great plasticity and differentiation potential that play a pivotal role in revascularization processes, i.e. angiogenesis and arteriogenesis. To gain more insight in the relevant developmental programs, we compared the full-genome mRNA expression profiles of several distinct human monocyte subpopulations previously identified based on surface marker expression. These included classical and non-classical, M1 and M2 macrophages, circulating angiogenic cells (CAC), and non-monocyte-derived endothelial colony-forming cells (ECFC). Their transcriptional profiles revealed distinct and overlapping gene expression signatures and pathways reminiscent of utilization of transcription factors driving polarization into the different monocytic phenotypes. Hierarchical cluster analysis revealed that CAC are most related to M2 macrophages and unstimulated macrophages, and to a lesser extent to classical monocytes, and are quite distinct from M1 macrophages and ECFC. Analysis of the promoter region of CAC-expressed genes suggests that in particular the ETS family of transcription factors is important in CAC development. These analyses show the power of combining multiple datasets with existing databases on biological knowledge, to interpret full genome expression data.


Nucleotide sequence of the kanamycin resistance determinant of the pneumococcal transposon Tn1545: evolutionary relationships and transcriptional analysis of aphA-3 genes.
The nucleotide sequence of the kanamycin resistance determinant aphA-3 encoded by transposon Tn1545 from Streptococcus pneumoniae was determined and compared to those of plasmids pJH1 and pIP1433 from Streptococcus faecalis and Campylobacter coli, respectively. The three sequences were found to be identical and differed by two substitutions and the deletion of a codon from that of plasmid pSH2 from Staphylococcus aureus. Comparison of the 5' noncoding sequences indicated that the regions containing the aphA-3 gene in pJH1 and in Tn1545 evolved independently by deletion from a sequence similar to that found in pIP1433. In the latter plasmid, aphA-3 is transcribed from a promoter, P1, which is flanked by two 12-base pair direct repeats. The rearrangement observed in pJH1 removed one of these recombinogenic sites and altered the -10 and 3' flanking sequences of P1. The promoter thus generated. P1', allows expression of similar level of kanamycin resistance as P1. However, fusion experiments carried out with a promotorless chloramphenicol acetyltransferase gene indicated that the canonical promoter P1 is significantly less efficient than P1'. From analysis of the thermodynamic properties of these promoters, we conclude that this difference in strength reflects the melting properties of the -10 sequences. The transition from pIP1433 to pJH1 may correspond to the progression of a molecule structurally unstable to a more stable one combined with the need to maintain an efficient promoter upstream of the aphA-3 gene. The deletion event in Tn1545, which occurred between the two 12-base pair directly repeated sequences, removed P1 in its entirety.(ABSTRACT TRUNCATED AT 250 WORDS)


Networking our science to characterize the state, vulnerabilities, and management opportunities of soil organic matter.
Soil organic matter (SOM) supports the Earth's ability to sustain terrestrial ecosystems, provide food and fiber, and retains the largest pool of actively cycling carbon. Over 75% of the soil organic carbon (SOC) in the top meter of soil is directly affected by human land use. Large land areas have lost SOC as a result of land use practices, yet there are compensatory opportunities to enhance productivity and SOC storage in degraded lands through improved management practices. Large areas with and without intentional management are also being subjected to rapid changes in climate, making many SOC stocks vulnerable to losses by decomposition or disturbance. In order to quantify potential SOC losses or sequestration at field, regional, and global scales, measurements for detecting changes in SOC are needed. Such measurements and soil-management best practices should be based on well established and emerging scientific understanding of processes of C stabilization and destabilization over various timescales, soil types, and spatial scales. As newly engaged members of the International Soil Carbon Network, we have identified gaps in data, modeling, and communication that underscore the need for an open, shared network to frame and guide the study of SOM and SOC and their management for sustained production and climate regulation.


RB reversibly inhibits DNA replication via two temporally distinct mechanisms.
The retinoblastoma (RB) tumor suppressor is a critical negative regulator of cellular proliferation. Repression of E2F-dependent transcription has been implicated as the mechanism through which RB inhibits cell cycle progression. However, recent data have suggested that the direct interaction of RB with replication factors or sites of DNA synthesis may contribute to its ability to inhibit S phase. Here we show that RB does not exert a cis-acting effect on DNA replication. Furthermore, the localization of RB was distinct from replication foci in proliferating cells. While RB activation strongly attenuated the RNA levels of multiple replication factors, their protein expression was not diminished coincident with cell cycle arrest. During the first 24 h of RB activation, components of the prereplication complex, initiation factors, and the clamp loader complex (replication factor C) remained tethered to chromatin. In contrast, the association of PCNA and downstream components of the processive replication machinery was specifically disrupted. This signaling from RB occurred in a manner dependent on E2F-mediated transcriptional repression. Following long-term activation of RB, we observed the attenuation of multiple replication factors, the complete cessation of DNA synthesis, and impaired replicative capacity in vitro. Therefore, functional distinctions exist between the "chronic" RB-mediated arrest state and the "acute" arrest state. Strikingly, attenuation of RB activity reversed both acute and chronic replication blocks. Thus, continued RB action is required for the maintenance of two kinetically and functionally distinct modes of replication inhibition.


Structural characterization of normal and mutant human steroid 17 alpha-hydroxylase genes: molecular basis of one example of combined 17 alpha-hydroxylase/17,20 lyase deficiency.
Steroid 17 alpha-hydroxylase (cytochrome P-450 17 alpha) catalyzes both 17 alpha-hydroxylation of pregnenolone and progesterone and 17,20-lysis of 17 alpha-hydroxypregnenolone and 17 alpha-hydroxyprogesterone. In the course of undertaking detailed investigation of the structure-function relationships which exist within this enzyme we have begun to elucidate the molecular basis of human deficiencies in either or both of these activities. Consequently we have determined the exonic structure of the human P-450 17 alpha gene as well as the sequences at the exon/intron boundaries and at the site of initiation of transcription. A single gene in the human genome encodes this protein, being the sole member of a unique gene family (P450XVII) within the P-450 supergene family. A protocol for exonic sequencing of the P-450 17 alpha gene has been established which permits structural analysis of the gene from patients having 17 alpha-hydroxylase and/or 17,20-lyase deficiency. This procedure has been applied to the mutant gene from one individual having combined 17 alpha-hydroxylase/17,20-lyase deficiencies. A four-base duplication is found in exon 8 producing a protein with an altered C-terminal amino acid sequence which results in loss of both enzymatic activities.


Nonpolar mutagenesis of the ipa genes defines IpaB, IpaC, and IpaD as effectors of Shigella flexneri entry into epithelial cells.
A 31-kb fragment of the large virulence plasmid of Shigella flexneri is necessary for bacterial entry into epithelial cells in vitro. One locus of this fragment encodes the IpaA, -B, -C, and -D proteins, which are the dominant antigens of the humoral immune response during shigellosis. To address the role of the ipa genes, which are clustered in an operon, we constructed a selectable cassette that does not affect transcription of downstream genes and used this cassette to inactivate the ipaB, ipaC, and ipaD genes. Each of these nonpolar mutants was defective in entry and lysis of the phagocytic vacuole but was not impaired in adhesion to the cells. We showed that, like IpaB and IpaC, IpaD is secreted into the culture supernatant and that none of these proteins is necessary for secretion of the other two. This result differentiates the Ipa proteins, which direct the entry process, from the Mxi and Spa proteins, which direct secretion of the Ipa proteins. Moreover, lack of either IpaB or IpaD resulted in the release of larger amounts of the other Ipa polypeptides into the culture medium, which indicates that, in addition to their role in invasion, IpaB and IpaD are each involved in the maintenance of the association of the Ipa proteins with the bacterium.


Comparison Conundrum and the Chamber of Visualizations: An Exploration of How Language Influences Visual Design.
The language for expressing comparisons is often complex and nuanced, making supporting natural language-based visual comparison a non-trivial task. To better understand how people reason about comparisons in natural language, we explore a design space of utterances for comparing data entities. We identified different parameters of comparison utterances that indicate what is being compared (i.e., data variables and attributes) as well as how these parameters are specified (i.e., explicitly or implicitly). We conducted a user study with sixteen data visualization experts and non-experts to investigate how they designed visualizations for comparisons in our design space. Based on the rich set of visualization techniques observed, we extracted key design features from the visualizations and synthesized them into a subset of sixteen representative visualization designs. We then conducted a follow-up study to validate user preferences for the sixteen representative visualizations corresponding to utterances in our design space. Findings from these studies suggest guidelines and future directions for designing natural language interfaces and recommendation tools to better support natural language comparisons in visual analytics.


The Unmaking of a Modern Synthesis: Noam Chomsky, Charles Hockett, and the Politics of Behaviorism, 1955-1965.
A familiar story about mid-twentieth-century American psychology tells of the abandonment of behaviorism for cognitive science. Between these two, however, lay a scientific borderland, muddy and much traveled. This essay relocates the origins of the Chomskyan program in linguistics there. Following his introduction of transformational generative grammar, Noam Chomsky (b. 1928) mounted a highly publicized attack on behaviorist psychology. Yet when he first developed that approach to grammar, he was a defender of behaviorism. His antibehaviorism emerged only in the course of what became a systematic repudiation of the work of the Cornell linguist C. F. Hockett (1916-2000). In the name of the positivist Unity of Science movement, Hockett had synthesized an approach to grammar based on statistical communication theory; a behaviorist view of language acquisition in children as a process of association and analogy; and an interest in uncovering the Darwinian origins of language. In criticizing Hockett on grammar, Chomsky came to engage gradually and critically with the whole Hockettian synthesis. Situating Chomsky thus within his own disciplinary matrix suggests lessons for students of disciplinary politics generally and--famously with Chomsky--the place of political discipline within a scientific life.


Association between TPH2 gene polymorphisms and attention deficit hyperactivity disorder in Korean children.
Attention deficit hyperactivity disorder (ADHD) is a common disorder of the school-age population. ADHD is a familial disorder and genetic studies estimate heritability at 80%-90%. The aim of the present study was to investigate the association between the genetic type and alleles for the TPH2 gene in Korean children with ADHD. The sample consisted of 142 ADHD children and 139 control children. We diagnosed ADHD according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). ADHD symptoms were evaluated with Conners' Parent Rating Scales and Dupaul Parent ADHD Rating Scales. Blood samples were taken from the 281 subjects, DNA was extracted from blood lymphocytes, and polymerase chain reaction was performed for TPH2 polymorphism. Alleles and genotype frequencies were compared using the chi-square test. We compared the allele and genotype frequencies of TPH2 gene polymorphism in the ADHD and control groups. This study showed that there was a significant correlation among the frequencies of the rs11179027 (odd ratio [OR]=2.12, 95% confidence interval [CI]=1.13-3.97, p=0.020) and rs1843809 (OR=0.48, 95% CI=0.24-0.97, p=0.040) of alleles of TPH2, but the final conclusions are not definite. Follow-up studies with larger patient or pure subgroups are expected. These results suggested that TPH2 might be related to ADHD symptoms.


Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection.
Hypoperfusion-induced thrombosis is an important mechanism for postsurgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia. Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-minute occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid-state NMR, and Morris water maze. The effects on infarct size by Edaravone application at different time points after tHI were also compared. Prophylactic administration of Edaravone (4.5 mg/kg×2, IP, 1 hour before and 1 hour after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size. Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis.


Adoption of Electronic Health Record Among Substance Use Disorder Treatment Programs: Nationwide Cross-Sectional Survey Study.
Electronic health record (EHR) systems have been shown to be associated with improvements in care processes, quality of care, and patient outcomes. EHR also has a crucial role in the delivery of substance use disorder (SUD) treatment and is considered important for addressing SUD crises, including the opioid epidemic. However, little is known about the adoption of EHR in SUD treatment programs or the organizational-level factors associated with the adoption of EHR in SUD treatment. We examined the adoption of EHR in SUD programs, with a focus on changes in adoption from 2014 to 2017, and identified organizational-level factors associated with EHR adoption. We used data from the 2014 and 2017 National Drug Abuse Treatment System Surveys. Our analysis included 1027 SUD programs (531 in 2014 and 496 in 2017). We used chi-square and Mann-Whitney U tests for categorical and continuous variables, respectively, to assess changes in EHR adoption, technology use, program, and client characteristics. We also investigated differences in characteristics and barriers to adoption by EHR adoption status (adopted EHR vs had not adopted or were planning to adopt EHR). We then conducted multivariate logistic regressions to examine internal and external factors associated with EHR adoption. The adoption of EHR increased significantly from 57.6% (306/531) in 2014 to 69.2% (343/496) in 2017 (P<.001), showing that nearly one-third (153/496, 30.8%) of SUD programs had not yet adopted an EHR system by 2017. We identified a significant increase in technology use and ownership by a parent company (P=.01 and P<.001) and a decrease in the percentage of uninsured patients in 2017 (P<.001), compared to 2014. Our analysis further showed significant differences by adoption status for three major barriers to adoption: (1) start-up costs, (2) ongoing financial costs, and (3) privacy or security concerns (P<.001). Programs that used computerized scheduling (adjusted odds ratio [AOR] 3.02, 95% CI 2.23-4.09) and billing systems (AOR 2.29, 95% CI 1.62-3.25) were more likely to adopt EHR. Similarly, ownership type, such as private nonprofit (AOR 1.86, 95% CI 1.31-2.65) and public (AOR 2.14, 95% CI 1.27-3.67), or interest in participating in a patient-centered medical home (AOR 1.93, 95% CI 1.29-2.92), were associated with an increased likelihood to adopt EHR. Overall, SUD programs were more likely to adopt an EHR system in 2017 compared to 2014 (AOR 1.44, 95% CI 1.07-1.94). Our findings highlighted that SUD programs may be on track to achieve widespread EHR adoption. However, there is a need for focused strategies, resources, and policies explicitly designed to systematically address barriers and tackle obstacles to expanding the adoption of EHR systems. These efforts must be holistic and address factors at multiple organizational levels.


Factors related to the utilization of prenatal care in Vietnam.
Data from the 1988 Vietnam Demographic and Health Survey and 1990 Vietnam Accessibility of Contraceptives Survey were used in this analysis of the influence of selected individual and community characteristics on the utilization of prenatal care in Vietnam. Specific analysis of the impact of availability of health services and other development characteristics of the community on utilization of prenatal care was done in a rural subsample. The woman's educational level and total number of living children were the most significant predictors of prenatal care utilization. Age independent of parity did not significantly affect the use of prenatal care. Rural women and women living in provinces with the highest infant mortality rates were significantly less likely to use prenatal services than their counterparts in the urban areas and provinces with low infant mortality rates. Non-physician health care providers were the main sources of prenatal care for women in both rural and urban areas.


Current Understanding of Dolichoarteriopathies of the Internal Carotid Artery: A Review.
Dolichoarteriopathies of the internal carotid artery (DICAs) are not uncommon, and although several studies have investigated DICAs, several questions regarding the etiology and best management course for DICAs remain unanswered. It is also difficult to correlate the occurrence of DICAs with the onset of clinical symptoms. Therefore, we surveyed the literature in PubMed and performed a review of DICAs to offer a comprehensive picture of our understanding of DICAs. We found that DICAs can be classified into three types, specifically tortuous, coiling and kinking, and are not associated with atherosclerotic risk factors. Cerebral hemodynamic changes are mainly associated with the degree of bending of DICAs. DICAs can result in symptoms of the brain and eyes due to insufficient blood supply and can co-occur with a pulsatile cervical mass, a pharyngeal bulge and pulsation. The diagnostic tools for the assessment of DICAs include Doppler ultrasonography, computed tomography angiography (CTA), magnetic resonance angiography (MRA) and digital subtraction angiography (DSA), and although DSA remains the gold standard, Doppler ultrasonography is a convenient method that provides useful data for the morphological evaluation of DICAs. CTA and MRA are efficient methods for detecting the morphology of the cervical segment of DICAs. Some DICAs should be treated surgically based on certain indications, and several methods, including correcting the bending or shortening of DICAs, have been developed for the treatment of DICAs. The appropriate treatment of DICAs results in good outcomes and is associated with low morbidity and mortality rates. However, despite the success of surgical reconstruction, an appropriate therapeutic treatment remains a subject of numerous debates due to the lack of multicentric, randomized, prospective studies.


An overview of methods for deriving the radiative transfer theory from the Maxwell equations. II: Approach based on the Dyson and Bethe-Salpeter equations.
In this paper, the vector radiative transfer equation is derived by means of the vector integral Foldy equations describing the electromagnetic scattering by a group of particles. By Assuming that in a discrete random medium the positions of the particles are statistically independent and by applying the Twersky approximation to the order-of-scattering expansion of the total field, we derive the Dyson equation for the coherent field and the ladder approximated Bethe-Salpeter equation for the dyadic correlation function. Then, under the far-field assumption for sparsely distributed particles, the Dyson equation is reduced to the Foldy integral equation for the coherent field, while the iterated solution of the Bethe-Salpeter equation ultimately yields the vector radiative transfer equation.