Grass pea natural variation reveals oligogenic resistance to Fusarium oxysporum f. sp. pisi.
Grass pea (Lathyrus sativus L.) is an annual legume species, phylogenetically close to pea (Pisum sativum L.), that may be infected by Fusarium oxysporum f. sp. pisi (Fop), the causal agent of fusarium wilt in peas with vast worldwide yield losses. A range of responses varying from high resistance to susceptibility to this pathogen has been reported in grass pea germplasm. Nevertheless, the genetic basis of that diversity of responses is still unknown, hampering its breeding exploitation. To identify genomic regions controlling grass pea resistance to fusarium wilt, a genome-wide association study approach was applied on a grass pea worldwide collection of accessions inoculated with Fop race 2. Disease responses were scored in this collection that was also subjected to high-throughput based single nucleotide polymorphisms (SNP) screening through genotyping-by-sequencing. A total of 5,651 high-quality SNPs were considered for association mapping analysis, performed using mixed linear models accounting for population structure. Because of the absence of a fully assembled grass pea reference genome, SNP markers' genomic positions were retrieved from the pea's reference genome v1a. In total, 17 genomic regions were associated with three fusarium wilt response traits in grass pea, anticipating an oligogenic control. Seven of these regions were located on pea chromosomes 1, 6, and 7. The candidate genes underlying these regions were putatively involved in secondary and amino acid metabolism, RNA (regulation of transcription), transport, and development. This study revealed important fusarium wilt resistance favorable grass pea SNP alleles, allowing the development of molecular tools for precision disease resistance breeding.


Temporal Dynamics of Co-circulating Lineages of Porcine Reproductive and Respiratory Syndrome Virus.
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the most important endemic pathogen in the U.S. swine industry. Despite control efforts involving improved biosecurity and different vaccination protocols, the virus continues to circulate and evolve. One of the foremost challenges in its control is high levels of genetic and antigenic diversity. Here, we quantify the co-circulation, emergence and sequential turnover of multiple PRRSV lineages in a single swine-producing region in the United States over a span of 9 years (2009-2017). By classifying over 4,000 PRRSV sequences (open-reading frame 5) into phylogenetic lineages and sub-lineages, we document the ongoing diversification and temporal dynamics of the PRRSV population, including the rapid emergence of a novel sub-lineage that appeared to be absent globally pre-2008. In addition, lineage 9 was the most prevalent lineage from 2009 to 2010, but its occurrence fell to 0.5% of all sequences identified per year after 2014, coinciding with the emergence or re-emergence of lineage 1 as the dominant lineage. The sequential dominance of different lineages, as well as three different sub-lineages within lineage 1, is consistent with the immune-mediated selection hypothesis for the sequential turnover in the dominant lineage. As host populations build immunity through natural infection or vaccination toward the most common variant, this dominant (sub-) lineage may be replaced by an emerging variant to which the population is more susceptible. An analysis of patterns of non- synonymous and synonymous mutations revealed evidence of positive selection on immunologically important regions of the genome, further supporting the potential that immune-mediated selection shapes the evolutionary and epidemiological dynamics for this virus. This has important implications for patterns of emergence and re-emergence of genetic variants of PRRSV that have negative impacts on the swine industry. Constant surveillance on PRRSV occurrence is crucial to a better understanding of the epidemiological and evolutionary dynamics of co-circulating viral lineages. Further studies utilizing whole genome sequencing and exploring the extent of cross-immunity between heterologous PRRS viruses could shed further light on PRRSV immunological response and aid in developing strategies that might be able to diminish disease impact.


Lactobacillus pentosus GMNL-77 inhibits skin lesions in imiquimod-induced psoriasis-like mice.
Psoriasis, which is regarded as a T-cell-mediated chronic inflammatory skin disease, is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes. In this study, we aimed to determine the in vivo effect of a potentially probiotic strain, Lactobacillus pentosus GMNL-77, in imiquimod-induced epidermal hyperplasia and psoriasis-like skin inflammation in BALB/c mice. Oral administration of L. pentosus GMNL-77 significantly decreased erythematous scaling lesions. Real-time polymerase chain reaction showed that treatment with L. pentosus GMNL-77 significantly decreased the mRNA levels of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6, and the IL-23/IL-17A axis-associated cytokines (IL-23, IL-17A/F, and IL-22) in the skin of imiquimod-treated mice. In addition, we found that L. pentosus GMNL-77 decreased the spleen weights of the imiquimod-treated group and reduced the numbers of IL-17- and IL-22-producing CD4+ T cells in the spleen. In conclusion, the present study provides insight into the potential use of L. pentosus GMNL-77 in the future treatment of psoriasis.


Normative Data for a Tablet-Based Dual-Task Assessment in Healthy Older Adults.
The objective of this study is to provide normative data for a tablet-based dual-task assessment in older adults without cognitive deficits. In total, 264 participants aged between 60 and 90 years, French and English-speaking, were asked to perform two discrimination tasks, alone and concurrently. The participants had to answer as fast as possible to one or two images appearing in the center of the tablet by pressing to the corresponding buttons. Normative data are provided for reaction time (RT), coefficient of variation, and accuracy. Analyses of variance were performed by trial types (single-pure, single-mixed, dual-mixed), and linear regressions assessed the relationship between performance and sociodemographic characteristics. The participants were highly educated and a large proportion of them were women (73.9%). The accuracy on the task was very high across all blocks. RT data revealed both a task-set cost and a dual-task cost between the blocks. Age was associated with slower RT and with higher coefficient of variability. Men were significantly slower on dual-mixed trials, but their coefficient of variability was lower on single-pure trials. Education was not associated with performance. This study provides normative data for a tablet-based dual-task assessment in older adults without cognitive impairment, which was lacking. All participants completed the task with good accuracy in less than 15 minutes and thus, the task is transferable to clinical and research settings.


Transfusion-associated graft-versus-host disease: report of an occurrence following the administration of irradiated blood.
Patients who are heavily immunosuppressed, such as those undergoing intensive anti-cancer chemotherapy, are at risk for development of accidental engraftment and graft-versus-host disease when they undergo transfusion with cellular blood components, a condition known as transfusion-associated graft-versus-host disease (TA-GVHD). To prevent this complication, it is routine to irradiate such blood components prior to their transfusion, although the minimum irradiation dose required is uncertain. The development of probable TA-GVHD is reported in a 10-year-old child following transfusions of platelets and packed red cells that had been irradiated at a nominal dose of 15 Gy. The transfusions were given during treatment for relapse of acute myeloid leukemia. Although the child developed complications including exfoliative dermatitis, delayed bone marrow regeneration, renal failure requiring dialysis, and respiratory failure requiring assisted respiration, she recovered from the episode of TA-GVHD after treatment with high-dose methylprednisolone and antithymocyte globulin. However, her leukemia relapsed, and she died. This experience suggests that the irradiation of cellular blood components at a nominal dose of 15 Gy prior to their transfusion to heavily immunosuppressed patients may be insufficient to prevent TA-GVHD.


Role of subtotal tonsillectomy ('tonsillotomy') in children with sleep disordered breathing.
Sleep disordered breathing in children causes disturbance in behaviour and also in cardiorespiratory and neurocognitive function. Subtotal tonsillectomy ('tonsillotomy') has been performed to treat sleep disordered breathing, with outcomes comparable to established therapies such as total tonsillectomy or adenoidectomy. This review critically assesses the role of subtotal tonsillectomy in a paediatric setting. The Medline database (1966 to October 2012) was electronically searched using key terms including subtotal or intracapsular tonsillectomy, tonsillotomy, tonsillectomy, paediatrics, and sleep disordered breathing. Eighteen papers were identified and reviewed. Subtotal tonsillectomy would appear to have an efficacy equal to that of total tonsillectomy for the treatment of sleep disordered breathing, and has significant benefits in reducing post-operative pain and analgesia use. Subtotal tonsillectomy patients appear to have less frequent post-operative haemorrhage compared with total tonsillectomy patients. In children, subtotal tonsillectomy is associated with fewer post-operative complications whilst having a comparable effect in improving sleep disordered breathing, compared with total tonsillectomy.


Cost-effectiveness of point-of-care C-reactive protein testing to inform antibiotic prescribing decisions.
Point-of-care C-reactive protein (POCCRP) is a biomarker of inflammation that offers clinicians a rapid POC test to guide antibiotic prescribing decisions for acute cough and lower respiratory tract infections (LRTI). However, evidence that POCCRP is cost-effective is limited, particularly outside experimental settings. To assess the cost-effectiveness of POCCRP as a diagnostic tool for acute cough and LRTI from the perspective of the health service. Observational study of the presentation, management, and outcomes of patients with acute cough and LRTI in primary care settings in Norway and Sweden. Using hierarchical regression, data were analysed in terms of the effect on antibiotic use, cost, and patient outcomes (symptom severity after 7 and 14 days, time to recovery, and EQ-5D), while controlling for patient characteristics (self-reported symptom severity, comorbidities, and health-related quality of life) at first attendance. POCCRP testing is associated with non-significant positive reductions in antibiotic prescribing (P = 0.078) and increased cost (P = 0.092). Despite the uncertainty, POCCRP testing is also associated with a cost per quality-adjusted life year (QALY) gain of €9391. At a willingness-to-pay threshold of €30,000 per QALY gained, there is a 70% probability of CRP being cost-effective. POCCRP testing is likely to provide a cost-effective diagnostic intervention both in terms of reducing antibiotic prescribing and in terms of QALYs gained.


Author self-citation in the diabetes literature.
Author self-citation is the practice of citing one's previous publications in a new publication. Its extent is unknown. We studied author self-citation, choosing the major clinical field of diabetes mellitus to represent the general medical literature. We identified every article about diabetes mellitus in 170 hand-searched clinical journals published in 2000. For every article, we recorded the bibliographic citation and publication type (original or review article) and assessed the methodologic rigour. Citation information was obtained from the ISI Web of Knowledge in April 2003. Of 49,028 articles, 289 were about diabetes mellitus and had citation information. Citation counts ranged from 0 to 347 (median 6, interquartile range [IQR] 2-12). Author self-citation counts ranged from 0 to 16 (median 1, IQR 0-2). Author self-citations accounted for an average of 18% (95% confidence interval [CI] 15%-21%) and a median of 7% (95% CI 5%- 11%) of all citations of each publication that was cited at least once (n = 266). Original articles had double the mean proportion of author self-citations compared with review articles (19% v. 9%; median 7% v. 0%, difference 7%, 95% CI 0- 10%). Methodologic rigour and review type were not significantly associated with subsequent author self-citation. Nearly one-fifth of all citations to articles about diabetes mellitus in clinical journals in the year 2000 were author self-citations. The frequency of self-citation was not associated with the quality of publications. These findings are likely applicable to the general clinical medicine literature and may have important implications for the assessment of journal or publication importance and the process of scientific discovery.


Racial Differences in Information Needs During and After Cancer Treatment: a Nationwide, Longitudinal Survey by the University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program.
Before treatment, cancer patients need information about side effects and prognosis, while after treatment they need information to transition to survivorship. Research documenting these needs is limited, especially among racial and ethnic minorities. This study evaluated cancer patients' needs according to race both before and after treatment. We compared white (n = 904) to black (n = 52) patients receiving treatment at 17 National Cancer Institute Community Oncology Research Program (NCORP) sites on their cancer-related concerns and need for information before and after cancer treatment. Two-sample t test and chi-squared analyses were used to assess group differences. Compared to white patients, black patients reported significantly higher concerns about diet (44.3 vs. 25.4 %,) and exercise (40.4 vs. 19.7 %,) during the course of treatment. Compared to whites, blacks also had significantly higher concern about treatment-related issues (white vs. black mean, 25.52 vs. 31.78), self-image issues (7.03 vs. 8.60), family-related issues (10.44 vs. 12.84), and financial concerns (6.42 vs. 8.90, all p < 0.05). Blacks, compared to whites, also had significantly greater post-treatment information needs regarding follow-up tests (8.17 vs. 9.44), stress management (4.12 vs. 4.89), and handling stigma after cancer treatment (4.21 vs. 4.89) [all p < 0.05]. Pre-treatment concerns and post-treatment information needs differed by race, with black patients reporting greater information needs and concerns. In clinical practice, tailored approaches may work particularly well in addressing the needs and concerns of black patients.


Success rate, healing time, and implant stability of photofunctionalized dental implants.
This is the first study to report the clinical outcomes of photofunctionalized dental implants. This retrospective study analyzed 95 consecutive patients who received 222 untreated implants and 70 patients who received 168 photofunctionalized implants over a follow-up period of 2.5 years. Photofunctionalization was performed by treating implants with UV light for 15 minutes using a photo device immediately before placement. The generation of superhydrophilicity and hemophilicity along with a substantial reduction in atomic percentage of surface carbon was confirmed after photofunctionalization. In both groups, 90% of the implants were placed in complex cases requiring staged or simultaneous site-development surgery. The implant stability was measured at implant placement and loading using the implant stability quotient (ISQ) values; then, the rate of implant stability development was evaluated by calculating the ISQ increase per month. The healing time before functional loading was 3.2 months in photofunctionalized implants and 6.5 months in untreated implants. The success rate was 97.6% and 96.3% for photofunctionalized and untreated implants, respectively. The ISQ increase per month for photofunctionalized implants ranged from 2.0 to 8.7 depending on the ISQ at placement, and it was considerably higher than that of untreated implants reported in the literature ranging from -1.8 to 2.8. Photofunctionalization resulted in a more frequent use of implants of 10 mm or shorter length and an overall decrease in implant diameter. Within the limits of this retrospective study, despite the more frequent use of shorter and smaller-diameter implants, the use of photofunctionalization allowed for a faster loading protocol without compromising the success rate. The outcome was associated with an increased rate of implant stability development. The results suggest that photofunctionalization may provide a novel and practical avenue to further advance implant therapy.


The Evolution of a Professional Practice Forum: Balancing Peer-to-Peer Learning With Course Objectives.
The Opioid Treatment Accreditation Course (OTAC) is a mandatory accreditation requirement in New South Wales, Australia, and aims to prepare medical practitioners for the provision of safe and effective Opioid Substitution Treatment to people with opioid dependence. The course has a strong focus on safe prescribing practices and the course design includes a Professional Practice Forum that is engaging for participants and effective at imparting complex ideas and concepts that do not place additional time constraints on already time-poor health professionals. The study aimed to use participatory action research methods to develop and evaluate an online Professional Practice Forum that is a key component of the OTAC teaching and learning experience. Three evaluation cycles were implemented with three cohorts of participants (N=40) to inform the design and review of the updated OTAC course. Overall, the study relied on participatory action research methods to enhance a sense of online community and to revise the Professional Practice Forum component of the course. Findings from survey feedback and an examination of Web metrics were used to monitor participant learning and were subsequently subject to thematic analysis in order to identify key themes. The use of participatory action techniques in the redesign of the OTAC course was a successful means of engaging with participants and resulted in four revisions based on feedback from facilitators and participants. The Professional Practice Forum was rated highly and received positive feedback from both moderators and participants. The use of interactive forums in online learning in an educational module for adult learners can prove extremely valuable as a means for participants to share their expertise and improve their learning outcomes. In particular, the use of sticky and welcome threads were significant features that enhanced interactions between participants and facilitators and resulted in increased quantity and quality of postings. These findings can help inform future researchers on how to develop peer engagement modules that are amenable to assessment and that build an online sense of community.


Personal and ambient exposures to air toxics in Camden, New Jersey.
Personal exposures and ambient concentrations of air toxics were characterized in a pollution "hot spot" and an urban reference site, both in Camden, New Jersey. The hot spot was the city's Waterfront South neighborhood; the reference site was a neighborhood, about 1 km to the east, around the intersection of Copewood and Davis streets. Using personal exposure measurements, residential ambient air measurements, statistical analyses, and exposure modeling, we examined the impact of local industrial and mobile pollution sources, particularly diesel trucks, on personal exposures and ambient concentrations in the two neighborhoods. Presented in the report are details of our study design, sample and data collection methods, data- and model-analysis approaches, and results and key findings of the study. In summary, 107 participants were recruited from nonsmoking households, including 54 from Waterfront South and 53 from the Copewood-Davis area. Personal air samples were collected for 24 hr and measured for 32 target compounds--11 volatile organic compounds (VOCs*), four aldehydes, 16 polycyclic aromatic hydrocarbons (PAHs), and particulate matter (PM) with an aerodynamic diameter < or = 2.5 microm (PM2.5). Simultaneously with the personal monitoring, ambient concentrations of the target compounds were measured at two fixed monitoring sites, one each in the Waterfront South and Copewood-Davis neighborhoods. To understand the potential impact of local sources of air toxics on personal exposures caused by temporal (weekdays versus weekend days) and seasonal (summer versus winter) variations in source intensities of the air toxics, four measurements were made of each subject, two in summer and two in winter. Within each season, one measurement was made on a weekday and the other on a weekend day. A baseline questionnaire and a time diary with an activity questionnaire were administered to each participant in order to obtain information that could be used to understand personal exposure to specific air toxics measured during each sampling period. Given the number of emission sources of air toxics in Waterfront South, a spatial variation study consisting of three saturation-sampling campaigns was conducted to characterize the spatial distribution of VOCs and aldehydes in the two neighborhoods. Passive samplers were used to collect VOC and aldehyde samples for 24- and 48-hr sampling periods simultaneously at 22 and 16 grid-based sampling sites in Waterfront South and Copewood-Davis, respectively. Results showed that measured ambient concentrations of some target pollutants (mean +/- standard deviation [SD]), such as PM2.5 (31.3 +/- 12.5 microg/m3), toluene (4.24 +/- 5.23 microg/m3), and benzo[a]pyrene (0.36 +/- 0.45 ng/m3), were significantly higher (P < 0.05) in Waterfront South than in Copewood-Davis, where the concentrations of PM2.5, toluene, and benzo[a]pyrene were 25.3 +/- 11.9 microg/m3, 2.46 +/- 3.19 microg/m3, and 0.21 +/- 0.26 ng/m3, respectively. High concentrations of specific air toxics, such as 60 microg/m3 for toluene and 159 microg/m3 for methyl tert-butyl ether (MTBE), were also found in areas close to local stationary sources in Waterfront South during the saturation-sampling campaigns. Greater spatial variation in benzene, toluene, ethylbenzene, and xylenes (known collectively as BTEX) as well as of MTBE was observed in Waterfront South than in Copewood-Davis during days with low wind speed. These observations indicated the significant impact of local emission sources of these pollutants and possibly of other pollutants emitted by individual source types on air pollution in Waterfront South. (Waterfront South is a known hot spot for these pollutants.) There were no significant differences between Waterfront South and Copewood-Davis in mean concentrations of benzene or MTBE, although some stationary sources of the two compounds have been reported in Waterfront South. Further, a good correlation (R > 0.6) was found between benzene and MTBE in both locations. These results suggest that automobile exhausts were the main contributors to benzene and MTBE air pollution in both neighborhoods. Formaldehyde and acetaldehyde concentrations were found to be high in both neighborhoods. Mean (+/- SD) concentrations of formaldehyde were 20.2 +/- 19.5 microg/m3 in Waterfront South and 24.8 +/- 20.8 microg/m3 in Copewood-Davis. A similar trend was observed for the two compounds during the saturation-sampling campaigns. The results indicate that mobile sources (i.e., diesel trucks) had a large impact on formaldehyde and acetaldehyde concentrations in both neighborhoods and that both are aldehyde hot spots. The study also showed that PM2.5, aldehydes, BTEX, and MTBE concentrations in both Waterfront South and Copewood-Davis were higher than ambient background concentrations in New Jersey and than national average concentrations, indicating that both neighborhoods are in fact hot spots for these pollutants. Higher concentrations were observed on weekdays than on weekend days for several compounds, including toluene, ethylbenzene, and xylenes (known collectively as TEX) as well as PAHs and PM2.5. These observations showed the impact on ambient air pollution of higher traffic volumes and more active industrial and commercial operations in the study areas on weekdays. Seasonal variations differed by species. Concentrations of TEX, for example, were found to be higher in winter than in summer in both locations, possibly because of higher emission rates from automobiles and reduced photochemical reactivity in winter. In contrast, concentrations of MTBE were found to be significantly higher in summer than in winter in both locations, possibly because of higher evaporation rates from gasoline in summer. Similarly, concentrations of heavier PAHs, such as benzo[a]pyrene, were found to be higher in winter in both locations, possibly because of higher emission rates from mobile sources, the use of home heating, and the reduced photochemical reactivity of benzo[a]pyrene in winter. In contrast, concentrations of lighter PAHs were found to be higher in summer in both locations, possibly because of volatilization of these compounds from various surfaces in summer. In addition, higher concentrations of formaldehyde were observed in summer than in winter, possibly because of significant contributions from photochemical reactions to formaldehyde air pollution in summer. Personal concentrations of toluene (25.4 +/- 13.5 microg/m3) and acrolein (1.78 +/- 3.7 microg/m3) in Waterfront South were found to be higher than those in the Copewood-Davis neighborhood (13.1 +/- 15.3 microg/m3 for toluene and 1.27 +/- 2.36 microg/m3 for acrolein). However, personal concentrations for most of the other compounds measured in Waterfront South were found to be similar to or lower than those than in Copewood-Davis. (For example, mean +/- SD concentrations were 4.58 +/- 17.3 microg/m3 for benzene, 4.06 +/- 5.32 microg/m3 for MTBE, 16.8 +/- 15.5 microg/m3 for formaldehyde, and 0.40 +/- 0.94 ng/m3 for benzo[a]pyrene in Waterfront South and 9.19 +/- 34.0 microg/m3 for benzene, 6.22 +/- 19.0 microg/m3 for MTBE, 16.0 +/- 16.7 microg/m3 for formaldehyde, and 0.42 +/- 1.08 ng/m3 for benzo[a]pyrene in Copewood-Davis.) This was probably because many of the target compounds had both outdoor and indoor sources. The higher personal concentrations of these compounds in Copewood-Davis might have resulted in part from higher exposure to environmental tobacco smoke (ETS) of subjects from Copewood-Davis. The Spearman correlation coefficient (R) was found to be high for pollutants with significant outdoor sources. The R's for MTBE and carbon tetrachloride, for example, were > 0.65 in both Waterfront South and Copewood-Davis. The R's were moderate or low (0.3-0.6) for compounds with both outdoor and indoor sources, such as BTEX and formaldehyde. A weaker association (R < 0.5) was found for compounds with significant indoor sources, such as BTEX, formaldehyde, PAHs, and PM2.5. The correlations between personal and ambient concentrations of MTBE and BTEX were found to be stronger in Waterfront South than in Copewood-Davis, reflecting the significant impact of local air pollution sources on personal exposure to these pollutants in Waterfront South. Emission-based ambient concentrations of benzene, toluene, and formaldehyde and contributions of ambient exposure to personal concentrations of these three compounds were modeled using atmospheric dispersion modeling and Individual Based Exposure Modeling (IBEM) software, respectively, which were coupled for analysis in the Modeling Environment for Total Risk (MENTOR) system. The compounds were associated with the three types of dominant sources in the two neighborhoods: industrial sources (toluene), exhaust from gasoline-powered motor vehicles (benzene), and exhaust from diesel-powered motor vehicles (formaldehyde). Subsequently, both the calculated and measured ambient concentrations of each of the three compounds were separately combined with the time diaries and activity questionnaires completed by the subjects as inputs to IBEM-MENTOR for estimating personal exposures from ambient sources. Modeled ambient concentrations of benzene and toluene were generally in agreement with the measured ambient concentrations within a factor of two, but the values were underestimated at the high-end percentiles. The major local (neighborhood) contributors to ambient benzene concentrations were from mobile sources in the study areas; both mobile and stationary (point and area) sources contributed to the ambient toluene concentrations. This finding can be used as guidance for developing better emission inventories to characterize, through modeling, the ambient concentrations of air toxics in the study areas. (ABSTRACT TRUNCATED)


Do popular media and internet-based hospital quality ratings identify hospitals with better cardiovascular surgery outcomes?
Several popular media and Internet-based hospital quality rankings have become increasingly publicized as a method for patients to choose better hospitals. It is unclear whether selecting highly rated hospitals will improve outcomes after cardiovascular surgery procedures. Using 2005 to 2006 Medicare data, we studied all patients undergoing abdominal aortic aneurysm repair, coronary artery bypass, aortic valve repair, and mitral valve repair (n = 312,813). Primary outcomes included risk-adjusted mortality, adjusting for patient characteristics and surgical acuity. We compared mortality at "Best Hospitals," according to US News and World Report and HealthGrades, with all other hospitals. We adjusted for hospital volume to determine whether hospital experience accounts for differences in mortality. Risk-adjusted mortality was considerably lower in US News and World Report's "Best Hospitals" for abdominal aortic aneurysm repair only (odds ratio [OR] = 0.76; 95% CI, 0.61 to 0.94). Risk-adjusted mortality was considerably lower in HealthGrades' "Best Hospitals" after all 4 procedures: abdominal aortic aneurysm repair (OR = 0.75; 95% CI, 0.58 to 0.97), coronary artery bypass (OR = 0.78; 95% CI, 0.68 to 0.89), aortic valve repair (OR = 0.71; 95% CI, 0.59 to 0.85), and mitral valve repair (OR = 0.77; 95% CI, 0.61 to 0.99). Accounting for hospital volume, risk-adjusted mortality was not substantially lower at the US News and World Report's "Best Hospitals," while risk-adjusted mortality was lower at HealthGrades' "Best Hospitals" after coronary artery bypass and aortic valve repair mortality rates were adjusted for hospital volume (OR = 0.77; 95% CI, 0.64 to 0.92 and OR = 0.81; 95% CI, 0.71 to 0.94). Popular hospital rating systems identify high-quality hospitals for cardiovascular operations. However, patients can experience equivalent outcomes by seeking care at high-volume hospitals.


miR-1343 attenuates pathways of fibrosis by targeting the TGF-β receptors.
Irreversible respiratory obstruction resulting from progressive airway damage, inflammation and fibrosis is a feature of several chronic respiratory diseases, including cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). The cytokine transforming growth factor β (TGF-β) has a pivotal role in promoting lung fibrosis and is implicated in respiratory disease severity. In the present study, we show that a previously uncharacterized miRNA, miR-1343, reduces the expression of both TGF-β receptor 1 and 2 by directly targeting their 3'-UTRs. After TGF-β exposure, elevated intracellular miR-1343 significantly decreases levels of activated TGF-β effector molecules, pSMAD2 (phosphorylated SMAD2) and pSMAD3 (phosphorylated SMAD3), when compared with a non-targeting control miRNA. As a result, the abundance of fibrotic markers is reduced, cell migration into a scratch wound impaired and epithelial-to-mesenchymal transition (EMT) repressed. Mature miR-1343 is readily detected in human neutrophils and HL-60 cells and is activated in response to stress in A549 lung epithelial cells. miR-1343 may have direct therapeutic applications in fibrotic lung disease.


The longitudinal relationship between behavior and emotional disturbance in young people with intellectual disability and maternal mental health.
Although elevated rates of parent psychosocial distress have been associated with child behavior and emotional problems, little is known about the nature of this relationship over time. This study followed an epidemiological cohort of children and adolescents over 11 years with 4 waves of data collection. Within this cohort, complete data were available on 238 mothers and their children. Behavior and emotional problems were assessed using the DBC, maternal mental health with the GHQ. Multivariate growth curve modelling was used to evaluate the commonality of individual change patterns. High levels of mental health problems were reported, which were stable over time. Higher scores on the DBC were associated with higher rates of mental health problems. Increases in child social relating problems were associated with increases mental health symptoms, particularly depression and anxiety.


A zirconium metal-organic framework with an exceptionally high volumetric surface area.
A zirconium metal-organic framework (MOF), PCN-111, has been synthesized by using an elongated ditopic carboxylate linker, 4,4'-(buta-1,3-diyne-1,4-diyl)dibenzoate. Single crystal X-ray diffraction characterization indicates that the noninterpenetrated microporous structure of PCN-111 is isoreticular to UIO MOFs with 12 connected Zr6O4(OH)4(CO2)12 clusters and a fcu topology. It was successfully activated through a solvent exchange with acetone followed by controlled evacuation and its gas sorption was reported. By using 77 K nitrogen adsorption isotherm and strictly applying three consistency criteria, the BET surface area for PCN-111 was calculated to be 4825 m2 g-1. Pore size distribution analysis suggests that the sizes of cavities contributing to nitrogen adsorption are predominately in the range of 15 to 20 Å, which are in good agreement with the two polyhedral cages (15.6 and 20.2 Å, respectively) in the single crystal X-ray solved structure. Owing to its relatively high crystal density (0.42 g cm-3), the volumetric surface area for PCN-111 was calculated to be 2026 m2 cm-3. The value is among the highest of all the reported ultrahigh surface area MOF materials. The exceptionally high microporosity of PCN-111 has also been validated by comparison with the simulated nitrogen adsorption isotherm derived from multipurpose simulation code MUSIC.


What are the benefits of interacting with nature?
There is mounting empirical evidence that interacting with nature delivers measurable benefits to people. Reviews of this topic have generally focused on a specific type of benefit, been limited to a single discipline, or covered the benefits delivered from a particular type of interaction. Here we construct novel typologies of the settings, interactions and potential benefits of people-nature experiences, and use these to organise an assessment of the benefits of interacting with nature. We discover that evidence for the benefits of interacting with nature is geographically biased towards high latitudes and Western societies, potentially contributing to a focus on certain types of settings and benefits. Social scientists have been the most active researchers in this field. Contributions from ecologists are few in number, perhaps hindering the identification of key ecological features of the natural environment that deliver human benefits. Although many types of benefits have been studied, benefits to physical health, cognitive performance and psychological well-being have received much more attention than the social or spiritual benefits of interacting with nature, despite the potential for important consequences arising from the latter. The evidence for most benefits is correlational, and although there are several experimental studies, little as yet is known about the mechanisms that are important for delivering these benefits. For example, we do not know which characteristics of natural settings (e.g., biodiversity, level of disturbance, proximity, accessibility) are most important for triggering a beneficial interaction, and how these characteristics vary in importance among cultures, geographic regions and socio-economic groups. These are key directions for future research if we are to design landscapes that promote high quality interactions between people and nature in a rapidly urbanising world.


Mathematical model for the cancer stem cell hypothesis.
Recent research on the origin of brain cancer has implicated a subpopulation of self-renewing brain cancer stem cells for malignant tumour growth. Various genes that regulate self-renewal in normal stem cells are also found in cancer stem cells. This implies that cancers can occur because of mutations in normal stem cells and early progenitor cells. A predictive mathematical model based on the cell compartment method is presented here to pose and validate non-intuitive scenarios proposed through the neural cancer stem cell hypothesis. The growths of abnormal (stem and early progenitor) cells from their normal counterparts are ascribed with separate mutation probabilities. Stem cell mutations are found to be more significant for the development of cancer than a similar mutation in the early progenitor cells. The model also predicts that, as previously hypothesized, repeated insult to mature cells increases the formation of abnormal progeny, and hence the risk of cancer.


Concerted regulation of npc2 binding to endosomal/lysosomal membranes by bis(monoacylglycero)phosphate and sphingomyelin.
Niemann-Pick Protein C2 (npc2) is a small soluble protein critical for cholesterol transport within and from the lysosome and the late endosome. Intriguingly, npc2-mediated cholesterol transport has been shown to be modulated by lipids, yet the molecular mechanism of npc2-membrane interactions has remained elusive. Here, based on an extensive set of atomistic simulations and free energy calculations, we clarify the mechanism and energetics of npc2-membrane binding and characterize the roles of physiologically relevant key lipids associated with the binding process. Our results capture in atomistic detail two competitively favorable membrane binding orientations of npc2 with a low interconversion barrier. The first binding mode (Prone) places the cholesterol binding pocket in direct contact with the membrane and is characterized by membrane insertion of a loop (V59-M60-G61-I62-P63-V64-P65). This mode is associated with cholesterol uptake and release. On the other hand, the second mode (Supine) places the cholesterol binding pocket away from the membrane surface, but has overall higher membrane binding affinity. We determined that bis(monoacylglycero)phosphate (bmp) is specifically required for strong membrane binding in Prone mode, and that it cannot be substituted by other anionic lipids. Meanwhile, sphingomyelin counteracts bmp by hindering Prone mode without affecting Supine mode. Our results provide concrete evidence that lipids modulate npc2-mediated cholesterol transport either by favoring or disfavoring Prone mode and that they impose this by modulating the accessibility of bmp for interacting with npc2. Overall, we provide a mechanism by which npc2-mediated cholesterol transport is controlled by the membrane composition and how npc2-lipid interactions can regulate the transport rate.


A Face-Aging Smoking Prevention/Cessation Intervention for Nursery School Students in Germany: An Appearance-Focused Interventional Study.
The Education Against Tobacco (EAT) network delivers smoking prevention advice in secondary schools, typically using the mirroring approach (i.e., a "selfie" altered with a face-aging app and shared with a class). In November 2017, however, the German assembly of EAT opted to expand its remit to include nursing students. To assess the transferability of the existing approach, we implemented it with the self-developed face-aging app "Smokerface" (=mixed - methods approach) in six nursing schools. Anonymous questionnaires were used to assess the perceptions of 197 students (age 18⁻40 years; 83.8% female; 26.4% smokers; 23.3% daily smokers) collecting qualitative and quantitative data for our cross-sectional study. Most students perceived the intervention to be fun (73.3%), but a minority disagreed that their own animated selfie (25.9%) or the reaction of their peers (29.5%) had motivated them to stop smoking. The impact on motivation not to smoke was considerably lower than experienced with seventh graders (63.2% vs. 42.0%; notably, more smokers also disagreed (45.1%) than agreed (23.5%) with this statement. Agreement rates on the motivation not to smoke item were higher in females than in males and in year 2⁻3 than in year 1 students. Potential improvements included greater focus on pathology (29%) and discussing external factors (26%). Overall, the intervention seemed to be appealing for nursing students.


Flotillins are involved in the polarization of primitive and mature hematopoietic cells.
Migration of mature and immature leukocytes in response to chemokines is not only essential during inflammation and host defense, but also during development of the hematopoietic system. Many molecules implicated in migratory polarity show uniform cellular distribution under non-activated conditions, but acquire a polarized localization upon exposure to migratory cues. Here, we present evidence that raft-associated endocytic proteins (flotillins) are pre-assembled in lymphoid, myeloid and primitive hematopoietic cells and accumulate in the uropod during migration. Furthermore, flotillins display a polarized distribution during immunological synapse formation. Employing the membrane lipid-order sensitive probe Laurdan, we show that flotillin accumulation in the immunological synapse is concomittant with membrane ordering in these regions. Together with the observation that flotillin polarization does not occur in other polarized cell types such as polarized epithelial cells, our results suggest a specific role for flotillins in hematopoietic cell polarization. Based on our results, we propose that in hematopoietic cells, flotillins provide intrinsic cues that govern segregation of certain microdomain-associated molecules during immune cell polarization.


N-Oct 5 is generated by in vitro proteolysis of the neural POU-domain protein N-Oct 3.
The neural POU-domain proteins N-Oct 3 and N-Oct 5 were first identified in electrophoretic mobility retardation assays through their ability to bind to the octamer sequence ATGCAAAT. These two N-Oct factors are detected in extracts from tumor-derived and normal neural cells. They are present differentially, however, in extracts from melanocytes and melanoma cells: N-Oct 3 is present in extracts from both melanocytes and melanoma cells, whereas N-Oct 5 is more evident in extracts from metastatic melanoma cells. We show here that a cDNA encoding N-Oct 3 directs synthesis of both the N-Oct 3 and N-Oct 5 proteins and that the N-Oct 5 protein in neural and melanoma-cell extracts is also related to N-Oct 3. N-Oct 5, however, is apparently not expressed in vivo: It is not detected if cells are rapidly lysed in SDS or if extracts are prepared with a cocktail of protease inhibitors that includes the serine-protease inhibitor 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF). These data suggest that N-Oct 5 is a specific in vitro proteolytic cleavage product of N-Oct 3 and is not directly related to melanocyte malignancy.


[How to implement Chile's new anti-tobacco law within the university].
On the 16th of May 2006, the Diario Oficial de la República de Chile (Official News of the Republic of Chile), published Law No. 20.105, which modified Law No. 19.419 regarding advertising and consumption of tobacco. Since it entered into force, different institutions and public spaces have had to enact its regulations. The purpose of this article is to share how the new anti-tobacco law is being implemented, with a health promotion angle, by the Pontificia Universidad Católica de Chile (UC). As such, we highlight key findings from a review of the literature on the subject and describe the implementation strategies developed and substantiated in theory as well as by how they address the concerns of the university community. The main accomplishments of the anti-tobacco implementation were: reaching a compromise between the university directorate and the student leaders, who in turn motivated the student body to participate during the large-scale roll-out of the new law; the participation of all of the UC stakeholders; utilizing the varied methods of mass communication; and lastly, providing an opportunity for reflection and analysis for those directly affected: the smokers. The challenge is to evaluate the strategies implemented in the incorporation of the new Chilean anti-tobacco law.


Association between genetic variants in myosin IXB and Crohn's disease.
Genetic variation in myosin IXB (MYO9B) was found to be associated with ulcerative colitis (UC) in a recent collaborative study. A nonsynonymous single nucleotide polymorphism (SNP) rs1545620 at the 3' end of the gene was found to be significantly associated with UC and weakly associated with Crohn's disease (CD). The aim of our current study was to replicate these findings in an independent UC cohort and to investigate association with CD. We also investigated subphenotype association and interactions with CARD15, IL23R, ATG16L1, and the IBD5 risk haplotype. In all, 652 CD patients, 650 UC patients, and 1190 controls were genotyped for 8 MYO9B SNPs. Haplotype testing, epistasis testing with known polymorphisms, and subphenotype analysis were performed. An intronic SNP rs2305767 in the MYO9B gene was associated with inflammatory bowel disease (IBD) overall (corrected P-value 0.002, odds ratio [OR] 0.76, 95% confidence interval [CI] 0.67-0.86). On individual disease analysis an association was found with CD (corrected P-value 0.001, OR 0.62, 95% CI 0.53-0.73) but not with UC. Analysis of the common MYO9B haplotypes showed significant association for CD and UC alone and IBD overall. No subphenotypic association was found. These data support an association between CD and SNPs in MYO9B independent of the established effects of SNPs in CARD15, IL23R, ATG16L1, and the IBD5 haplotype. There was no evidence of epistasis between SNPs in MYO9B and these established genes. MYO9B variants may be involved in IBD pathogenesis.


Therapeutic utilization of meditation resources by people with multiple sclerosis: insights from an online patient discussion forum.
We aimed to describe website traffic and qualitatively analyze an e-health community discussion forum. Participants in this study were people affected by multiple sclerosis visiting the Overcoming Multiple Sclerosis (OMS) website. This mixed methods study combined descriptive analysis of website traffic over 7 years and 1 month, and qualitative analysis of 1 week of posts in the meditation topic, coded into theme groups using qualitative thematic analysis. There were 166 meditation topics posted with 21,530 initial views of primary post and 785 sub-post responses. Meditation posts and sub-posts received 368,713 replies. Number of views increased from 4,684 in 2011 to over 80,000 in 2017, a considerably greater rate of increase than overall traffic. Qualitative analysis of posts on the meditation forum identified themes of barriers and enablers to utilization of meditation resources. Enablement themes dominated, observed across six of the seven theme groups with various forms of positive social and emotional support to learn and practice meditation. One theme, negative emotion, was identified as a barrier. The OMS peer-to-peer patient online discussion forum serves important functions in encouraging, educating and enabling its growing online community. Our analysis may help improve and innovate online support for lifestyle management in many chronic diseases.


The feather holes on the barn swallow Hirundo rustica and other small passerines are probably caused by Brueelia spp. lice.
Barn swallows Hirundo rustica often have characteristic feather holes on wing and tail feathers. During the past 15 yr, several influential papers have been based on the assumption that these holes were chewed by the louse Machaerilaemus malleus. We gathered feather-hole data from barn swallows and other passerines at 2 sites in Hungary and correlated the presence of holes with louse infestations and, more specifically, with the occurrence of M. malleus versus other species of avian lice. The shape of frequency distribution of holes was left-biased, and this bias was more pronounced in large swallow colonies that in a random sample, in accordance with the view that the causative agent of the 'feather hole symptom' is a contagious macroparasite. However, both intra- and interspecific comparisons suggest that the causative agent of the symptom had probably been misidentified. The occurrence of Brueelia spp. 'wing lice' provides the best fit to the distribution and abundance of feather holes, both in barn swallows and across some other small passerines. This identification error does not challenge the results of the former evolutionary-ecological studies based on this model system, although it has important implications from the viewpoint of louse biology.


Polymerase η suppresses telomere defects induced by DNA damaging agents.
Telomeres at chromosome ends are normally masked from proteins that signal and repair DNA double strand breaks (DSBs). Bulky DNA lesions can cause DSBs if they block DNA replication, unless they are bypassed by translesion (TLS) DNA polymerases. Here, we investigated roles for TLS polymerase η, (polη) in preserving telomeres following acute physical UVC exposure and chronic chemical Cr(VI) exposure, which both induce blocking lesions. We report that polη protects against cytotoxicity and replication stress caused by Cr(VI), similar to results with ultraviolet C light (UVC). Both exposures induce ataxia telangiectasia and Rad3-related (ATR) kinase and polη accumulation into nuclear foci and localization to individual telomeres, consistent with replication fork stalling at DNA lesions. Polη-deficient cells exhibited greater numbers of telomeres that co-localized with DSB response proteins after exposures. Furthermore, the genotoxic exposures induced telomere aberrations associated with failures in telomere replication that were suppressed by polη. We propose that polη's ability to bypass bulky DNA lesions at telomeres is critical for proper telomere replication following genotoxic exposures.


Nanoscale biophysical properties of the cell surface galactosaminogalactan from the fungal pathogen Aspergillus fumigatus.
Many fungal pathogens produce cell surface polysaccharides that play essential roles in host-pathogen interactions. In Aspergillus fumigatus, the newly discovered polysaccharide galactosaminogalactan (GAG) mediates adherence to a variety of substrates through molecular mechanisms that are poorly understood. Here we use atomic force microscopy to unravel the localization and adhesion of GAG on living fungal cells. Using single-molecule imaging with tips bearing anti-GAG antibodies, we found that GAG is massively exposed on wild-type (WT) germ tubes, consistent with the notion that this glycopolymer is secreted by the mycelium of A. fumigatus, while it is lacking on WT resting conidia and on germ tubes from a mutant (Δuge3) deficient in GAG. Imaging germ tubes with tips bearing anti-β-glucan antibodies shows that exposure of β-glucan is strongly increased in the Δuge3 mutant, indicating that this polysaccharide is masked by GAG during hyphal growth. Single-cell force measurements show that expression of GAG on germ tubes promotes specific adhesion to pneumocytes and non-specific adhesion to hydrophobic substrates. These results provide a molecular foundation for the multifunctional adhesion properties of GAG, thus suggesting it could be used as a potential target in anti-adhesion therapy and immunotherapy. Our methodology represents a powerful approach for characterizing the nanoscale organization and adhesion of cell wall polysaccharides during fungal morphogenesis, thereby contributing to increase our understanding of their role in biofilm formation and immune responses.


"The problem is ours, it is not CRAIDS' ". Evaluating sustainability of Community Based Organisations for HIV/AIDS in a rural district in Zambia.
While sustainability of health programmes has been the subject of empirical studies, there is little evidence specifically on the sustainability of Community Based Organisations (CBOs) for HIV/AIDS. Debates around optimal approaches in community health have centred on utilitarian versus empowerment approaches. This paper, using the World Bank Multi-Country AIDS Program (MAP) in Zambia as a case study, seeks to evaluate whether or not this global programme contributed to the sustainability of CBOs working in the area of HIV/AIDS in Zambia. Lessons for optimising sustainability of CBOs in lower income countries are drawn. In-depth interviews with representatives of all CBOs that received CRAIDS funding (n = 18) and district stakeholders (n= 10) in Mumbwa rural district in Zambia, in 2010; and national stakeholders (n=6) in 2011. All eighteen CBOs in Mumbwa that received MAP funding between 2003 and 2008 had existed prior to receiving MAP grants, some from as early as 1992. This was contrary to national level perceptions that CBOs were established to access funds rather than from the needs of communities. FUNDING opportunities for CBOs in Mumbwa in 2010 were scarce.Health services: While all CBOs were functioning in 2010, most reported reductions in service provision. Home visits had reduced due to a shortage of food to bring to people living with HIV/AIDS and scarcity of funding for transport, which reduced antiretroviral treatment adherence support and transport of patients to clinics.Organisational capacity and viability: Sustainability had been promoted during MAP through funding Income Generating Activities. However, there was a lack of infrastructure and training to make these sustainable. Links between health facilities and communities improved over time, however volunteers' skills levels had reduced. Whilst the World Bank espoused the idea of sustainability in their plans, it remained on the periphery of their Zambia strategy. Assessments of need on the ground and accurate costings for sustainable service delivery, building on existing community strengths, are needed before projects commence. This study highlights the importance of enabling and building the capacity of existing CBOs and community structures, rather than creating new mechanisms.


Global research partnerships in advancing public health: A case study on India.
Collaborative research is integral to medicine. Multi-national and multi-institutional research partnerships produce advances in medicine and public health that have a significant societal impact. Developing nations can gain from such collaborative partnerships in achieving progress in sustainable development goals. However, it is important that the research agenda is relevant to the region where studies are conducted. Funding of research by the national government and regional organisations will ensure that the research is appropriate for the region, and ethically rigorous. In this study, I investigated the characteristics of research partnerships in India, especially the sources of research funding.


The Hippo pathway controls border cell migration through distinct mechanisms in outer border cells and polar cells of the Drosophila ovary.
The Hippo pathway is a key signaling cascade in controlling organ size. The core components of this pathway are two kinases, Hippo (Hpo) and Warts (Wts), and a transcriptional coactivator, Yorkie (Yki). Yes-associated protein (YAP, a Yki homolog in mammals) promotes epithelial-mesenchymal transition and cell migration in vitro. Here, we use border cells in the Drosophila ovary as a model to study Hippo pathway functions in cell migration in vivo. During oogenesis, polar cells secrete Unpaired (Upd), which activates JAK/STAT signaling of neighboring cells and specifies them into outer border cells. The outer border cells form a cluster with polar cells and undergo migration. We find that hpo and wts are required for migration of the border cell cluster. In outer border cells, overexpression of hpo disrupts polarization of the actin cytoskeleton and attenuates migration. In polar cells, knockdown of hpo and wts or overexpression of yki impairs border cell induction and disrupts migration. These manipulations in polar cells reduce JAK/STAT activity in outer border cells. Expression of upd-lacZ is increased and decreased in yki and hpo mutant polar cells, respectively. Furthermore, forced expression of upd in polar cells rescues defects of border cell induction and migration caused by wts knockdown. These results suggest that Yki negatively regulates border cell induction by inhibiting JAK/STAT signaling. Together, our data elucidate two distinct mechanisms of the Hippo pathway in controlling border cell migration: (1) in outer border cells, it regulates polarized distribution of the actin cytoskeleton; (2) in polar cells, it regulates upd expression to control border cell induction and migration.


Exploring the neural substrates of attentional control and human intelligence: Diffusion tensor imaging of prefrontal white matter tractography in healthy cognition.
We combined diffusion tension imaging (DTI) of prefrontal white matter integrity and neuropsychological measures to examine the functional neuroanatomy of human intelligence. Healthy participants completed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) along with neuropsychological tests of attention and executive control, as measured by Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST). Stochastic tractography, considered the most effective DTI method, quantified white matter integrity of the medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) circuitry. Based on prior studies, we hypothesized that posterior mOFC-rACC connections may play a key structural role linking attentional control processes and intelligence. Behavioral results provided strong support for this hypothesis, specifically linking attentional control processes, measured by Trails B and WCST perseverative errors, to intelligent quotient (IQ). Hierarchical regression results indicated left posterior mOFC-rACC fractional anisotropy (FA) and Trails B performance time, but not WCST perseverative errors, each contributed significantly to IQ, accounting for approximately 33.95-51.60% of the variance in IQ scores. These findings suggested that left posterior mOFC-rACC white matter connections may play a key role in supporting the relationship of executive functions of attentional control and general intelligence in healthy cognition.


Evidence-based medicine and the law: the courts confront clinical practice guidelines.
This article examines how courts are likely to apply evidence-based medicine, and particularly clinical practice guidelines (CPGs), in healthcare litigation involving quality-of-care and entitlement-to-benefits (coverage) claims. Exploring the "politics" of the current situation, it observes that, just as clinicians have been reluctant to use CPGs in practice, courts have been, and likely will continue to be, slow to apply them in deciding cases., The article analyzes extant and proposed statutory approaches to legitimizing and promoting courts' use of CPGs. It concludes by renewing the author's earlier and controversial proposal to establish a voluntary federal program for certifying guidelines and directing courts to give certified CPGs greater weight in healthcare litigation.


Icosahedral AlCuFe quasicrystal at high pressure and temperature and its implications for the stability of icosahedrite.
The first natural-occurring quasicrystal, icosahedrite, was recently discovered in the Khatyrka meteorite, a new CV3 carbonaceous chondrite. Its finding raised fundamental questions regarding the effects of pressure and temperature on the kinetic and thermodynamic stability of the quasicrystal structure relative to possible isochemical crystalline or amorphous phases. Although several studies showed the stability at ambient temperature of synthetic icosahedral AlCuFe up to ~35 GPa, the simultaneous effect of temperature and pressure relevant for the formation of icosahedrite has been never investigated so far. Here we present in situ synchrotron X-ray diffraction experiments on synthetic icosahedral AlCuFe using multianvil device to explore possible temperature-induced phase transformations at pressures of 5 GPa and temperature up to 1773 K. Results show the structural stability of i-AlCuFe phase with a negligible effect of pressure on the volumetric thermal expansion properties. In addition, the structural analysis of the recovered sample excludes the transformation of AlCuFe quasicrystalline phase to possible approximant phases, which is in contrast with previous predictions at ambient pressure. Results from this study extend our knowledge on the stability of icosahedral AlCuFe at higher temperature and pressure than previously examined, and provide a new constraint on the stability of icosahedrite.


Advances on erythrocyte-mimicking nanovehicles to overcome barriers in biological microenvironments.
Although nanocarriers offer many advantages as drug delivery systems, their poor stability in circulation, premature drug release and nonspecific uptake in non-target organs have prompted biomimetic approaches using natural cell membranes to camouflage nanovehicles. Among them, erythrocytes, representing the most abundant blood circulating cells, have been extensively investigated for biomimetic coating on artificial nanocarriers due to their upgraded biocompatibility, biodegradability, non-immunogenicity and long-term blood circulation. Due to the cell surface mimetic properties combined with customized core material, erythrocyte-mimicking nanovehicles (EM-NVs) have a wide variety of applications, including drug delivery, imaging, phototherapy, immunomodulation, sensing and detection, that foresee a huge potential for therapeutic and diagnostic applications in several diseases. In this review, we summarize the recent advances in the biomedical applications of EM-NVs in cancer, infection, heart-, autoimmune- and CNS-related disorders and discuss the major challenges and opportunities in this research area.


Positive predictive value of device-detected atrial high-rate episodes at different rates and durations: an analysis from ASSERT.
Pacemakers can automatically identify and catalog atrial high-rate episodes (AHREs). While most AHREs represent true atrial tachyarrhythmia/atrial fibrillation (AT/AF), a review of stored electrograms suggests that a substantial proportion do not. As AHREs may lead to the initiation of oral anticoagulation, it is crucial to understand the relationship between AHREs and true AT/AF. To compare the positive predictive value of AHREs for electrogram-confirmed AT/AF for various atrial rates and episode durations. By using data from 2580 patients who participated in the ASymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the AF Reduction atrial pacing Trial, all AHREs >6 minutes and >190 beats/min with available electrograms were reviewed to determine whether they represented true AT/AF. The positive predictive value of these AHREs was assessed for episode durations of 6 minutes, 30 minutes, 6 hours, and 24 hours at atrial rates of 190 and 250 beats/min. Of 5769 AHREs >6 minutes and >190 beats/min, 82.7% were true AT/AF and 17.3% were false positives (predominantly due to repetitive non-re-entrant ventriculoatrial synchrony). False positives dropped to 6.8%, 3.3%, and 1.8% when the threshold duration was increased to 30 minutes, 6 hours, and 24 hours, respectively. Increasing the threshold heart rate to 250 beats/min added little to the positive predictive value when longer threshold durations were used. By using a cutoff of >6 minutes and >190 beats/min, the rate of false-positive AHREs is 17.3%, making physician review of electrograms essential. For AHREs lasting >6 hours, the rate of false positives is 3.3%, making physician review less crucial.


Longitudinal assessment of occupational exposures to the organophosphorous insecticides chlorpyrifos and profenofos in Egyptian cotton field workers.
Chlorpyrifos (CPF) and profenofos (PFF) are organophosphorus (OP) insecticides that are applied seasonally in Egypt to cotton fields. Urinary trichloro-2-pyridinol (TCPy), a specific CPF metabolite, and 4-bromo-2-chlorophenol (BCP), a specific PFF metabolite, are biomarkers of exposure, while inhibition of blood butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) activities are effect biomarkers that may be associated with neurotoxicity. Urinary TCPy and BCP and blood BChE and AChE activities were measured in 37 adult Egyptian Ministry of Agriculture workers during and after 9-17 consecutive days of CPF application followed by an application of PFF (9-11 days), and a second CPF application (5 days) in 2008. During the OP applications, urinary TCPy and BCP levels were significantly higher than baseline levels, remained elevated following the application periods, and were associated with an exposure related inhibition of blood BChE and AChE. Analysis of blood AChE levels before and after the PFF application period suggests that individual workers with peak BCP levels greater than 1000 μg/g creatinine exhibited further inhibition of blood AChE with PFF application, demonstrating that PFF exposure had a negative impact on AChE activity in this highly exposed worker population. While large interindividual differences in exposure were observed throughout this longitudinal study (peak urinary BCP and peak TCPy levels for individuals ranging from 13.4 to 8052 and 16.4 to 30,107 μg/g creatinine, respectively), these urinary biomarkers were highly correlated within workers (r=0.75, p<0.001). This suggests that the relative exposures to CPF and PFF were highly correlated for a given worker. The variable exposures between job classification and work site suggest that job title and work location should not be used as the sole basis for categorizing OP exposures when assessing neurobehavioral and other health outcomes in Egyptian cotton field workers. Together, these findings will be important in educating the Egyptian insecticide application workers in order to encourage the development and implementation of work practices and personal protective equipment to reduce their exposure to CPF and PFF.


Pre-Sleep Cognitive Arousal Is Negatively Associated with Sleep Misperception in Healthy Sleepers during Habitual Environmental Noise Exposure: An Actigraphy Study.
Specific noises (e.g., traffic or wind turbines) can disrupt sleep and potentially cause a mismatch between subjective sleep and objective sleep (i.e., "sleep misperception"). Some individuals are likely to be more vulnerable than others to noise-related sleep disturbances, potentially as a result of increased pre-sleep cognitive arousal. The aim of the present study was to examine the relationships between pre-sleep cognitive arousal and sleep misperception. Sixteen healthy sleepers participated in this naturalistic, observational study. Three nights of sleep were measured using actigraphy, and each 15-s epoch was classified as sleep or wake. Bedside noise was recorded, and each 15-s segment was classified as containing noise or no noise and matched to actigraphy. Participants completed measures of habitual pre-sleep cognitive and somatic arousal and noise sensitivity. Pre-sleep cognitive and somatic arousal levels were negatively associated with subjective−objective total sleep time discrepancy (p < 0.01). There was an association between sleep/wake and noise presence/absence in the first and last 90 min of sleep (p < 0.001). These results indicate that higher levels of habitual pre-sleep arousal are associated with a greater degree of sleep misperception, and even in healthy sleepers, objective sleep is vulnerable to habitual bedside noise.


The genetical and environmental determination of phally polymorphism in the freshwater snail Bulinus truncatus.
In some species of self-fertile pulmonate snails, two sexual morphs co-occur in natural populations: regular individuals and aphallic individuals that cannot transmit sperm to other snails. Purely aphallic populations therefore reproduce obligatorily by selfing. Understanding the evolution of aphally and selfing in these snails requires a precise knowledge of phally determination. In this paper, we investigate the genetic and environmental determination of aphally in Bulinus truncatus by a survey of the family (offspring) aphally ratio of 233 individuals originating from seven natural populations and a study of the reaction norm of the family aphally ratio to temperature using 60 individuals from 10 selfed lineages of one population. Our results indicate a high genetic variability for the determination of aphally between populations and within some populations, associated with a high level of genetic determination. Our second experiment indicates a significant temperature and lineage effect though no interaction between these two effects. We discuss our results in the framework of threshold models developed for dimorphic traits with polygenic inheritance. We propose that the sexual morph of an individual at a given temperature is determined by a temperature threshold value depending on both the individual genotype and probabilistic processes.


Control of translocation through the Sec61 translocon by nascent polypeptide structure within the ribosome.
During polytopic protein biogenesis, multiple transmembrane segments (TMs) must pass through the ribosome exit tunnel and into the Sec61 translocon prior to insertion into the endoplasmic reticulum membrane. To investigate how movement of a newly synthesized TM along this integration pathway might be influenced by synthesis of a second TM, we used photocross-linking probes to detect the proximity of ribosome-bound nascent polypeptides to Sec61alpha. Probes were inserted at sequential sites within TM2 of the aquaporin-1 water channel by in vitro translation of truncated mRNAs. TM2 first contacted Sec61alpha when the probe was positioned approximately 38 residues from the ribosome peptidyltransferase center, and TM2-Sec61alpha photoadducts decreased markedly when the probe was >80 residues from the peptidyltransferase center. Unexpectedly, as nascent chain length was gradually extended, photocross-linking at multiple sites within TM2 abruptly and transiently decreased, indicating that TM2 initially entered, withdrew, and then re-entered Sec61alpha. This brief reduction in TM2 photocross-linking coincided with TM3 synthesis. Replacement of TM3 with a secretory reporter domain or introduction of proline residues into TM3 changed the TM2 cross-linking profile and this biphasic behavior. These findings demonstrate that the primary and likely secondary structure of the nascent polypeptide within the ribosome exit tunnel can influence the timing with which topogenic determinants contact, enter, and pass through the translocon.


What do people with psychosis think caused their psychosis? A Q methodology study.
A key component of cognitive therapy for psychosis is the development of a meaningful and shared formulation of the onset of the psychosis. Therapists bring an understanding of the development of psychotic symptoms based on theoretical models and try to marry these with the person's own experience and explanations. However, an important question is whether this understanding is compatible with the explanations held by the client. This study investigated what factors people believed led to the onset of their psychosis. A Q set of potential causes for psychosis was identified from a literature search and interviews with people with differing experiences of psychosis. From this, 58 potential causes of psychosis were identified. Twenty-one people who had experienced a psychotic breakdown then ranked these explanations as possible causes. Using Principle Components Analysis four main factors were identified as perceived causal factors for the onset of psychosis. These factors were described as: a) drug usage; b) traumatic experiences in adulthood; c) personal sensitivity; and d) developmental vulnerabilities. This study revealed that people with psychosis have different explanatory frameworks for the onset of their difficulties. This work is helpful as this effort to understand the person's own understanding of their problems is a first stepping stone towards a collaboratively generated formulation that may be helpful in building a therapeutic alliance, engagement in treatment, and ultimately in improved outcome. It is likely that these different explanatory frameworks could lend themselves to different treatment approaches.


Expression of a novel gene product by transplants of genetically modified primary fibroblasts in the central nervous system.
Primary fibroblasts initiated from skin biopsies of Wistar rats were transfected with a plasmid that encodes the human growth hormone and the neomycin resistance genes. Cell clones selected for G418 resistance and expressing high levels of human growth hormone were propagated in vitro and subsequently transplanted into the cerebral cortex of adult allogeneic rats. Grafts were examined by immunocytochemistry at weekly intervals up to 2 months. Fibroblasts in the transplants survived and expressed growth hormone clearly up to 4 weeks, but showed reduced expression at 6 to 8 weeks. Significant levels of human growth hormone were also detected by radioimmunoassay in the serum of the host rats up to 1 month. The experiments demonstrate that primary fibroblasts can be genetically modified to deliver a new gene product into the central nervous system, and the gene product can pass the blood-brain barrier to enter the systemic circulation. This model illustrates the potential to introduce desired products into the brain through the genetic alteration of autologous primary fibroblasts.


Effect of single-dose rituximab on primary glomerular diseases.
A paradigm shift from such toxic 'nonspecific' therapies to selective immunomodulating regimens is necessary for glomerular diseases. Rituximab, which acts by inhibiting CD20-mediated B cell proliferation and differentiation, could be effective in the treatment of nephrotic syndrome as shown in recent reports. To assess the effects of rituximab in patients with primary glomerular diseases, including minimal-change disease, immunoglobulin A (IgA) nephropathy, focal segmental glomerulonephritis, membranous nephropathy and membranoproliferative glomerulonephritis, we performed a prospective trial of the effects of single-dose rituximab therapy in 24 patients. We prospectively evaluated the serum and urinary biochemical parameters before and after 6 months of therapy. In all of the patients studied, depletion of CD19 and CD20 cells was noted, with significant reduction in the degree of proteinuria from 3.7 ± 3.4 g/day at baseline to 1.3 ± 2.0 g/day at 6 months after the drug administration (p = 0.002). However, no significant changes of the serum creatinine, urinary RBC sediment, serum CD4/8 or serum IL-4 levels were observed at 6 months after the drug administration. In subjects with IgA nephropathy, while depletion of CD19 and CD20 cells was noted, no significant change in the severity of proteinuria was observed at 6 months after the drug administration as compared with the level at the baseline. For the treatment of primary glomerular diseases, the use of a single dose of rituximab is demonstrated with no serious adverse events. Further study of the mechanism of action of rituximab in successfully treated patients could encourage new perspectives in the treatment of primary glomerular diseases.


Impact of Incident Cancer on Short-Term Coronary Artery Disease-Related Healthcare Expenditures Among Medicare Beneficiaries.
Background: Healthcare spending for coronary artery disease (CAD)-related services is higher than for other chronic conditions. Diagnosis of incident cancer may impede management of CAD, thereby increasing the risk of CAD-related complications and associated healthcare expenditures. This study examined the relationship between incident cancer and CAD-related expenditures among elderly Medicare beneficiaries. Patients and Methods: A retrospective longitudinal study was conducted using the SEER-Medicare linked registries and a 5% noncancer random sample of Medicare beneficiaries. Elderly fee-for-service Medicare beneficiaries with preexisting CAD and with incident breast, colorectal, or prostate cancer (N=12,095) or no cancer (N=34,237) were included. CAD-related healthcare expenditures comprised Medicare payments for inpatient, home healthcare, and outpatient services. Expenditures were measured every 120 days during the 1-year preindex and 1-year postindex periods. Adjusted relationship between incident cancer and expenditures was analyzed using the generalized linear mixed models. Results: Overall, CAD-related mean healthcare expenditures in the preindex period accounted for approximately 32.6% to 39.5% of total expenditures among women and 41.5% to 46.8% among men. All incident cancer groups had significantly higher CAD-related expenditures compared with noncancer groups (P<.0001). Men and women with colorectal cancer (CRC) had 166% and 153% higher expenditures, respectively, compared with their noncancer counterparts. Furthermore, men and women with CRC had 57% and 55% higher expenditures compared with those with prostate or breast cancer, respectively. Conclusions: CAD-related expenditures were higher for elderly Medicare beneficiaries with incident cancer, specifically for those with CRC. This warrants the need for effective programs and policies to reduce CAD-related expenditures. Close monitoring of patients with a cancer diagnosis and preexisting CAD may prevent CAD-related events and expenditures.


Ex vivo expansion of regulatory T cells from abdominal aortic aneurysm patients inhibits aneurysm in humanized murine model.
Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease. Studies of human aneurysm tissue demonstrate dense inflammatory cell infiltrates with CD4+ T cells predominating. Regulatory T cells (Tregs) play an important role in inhibiting pro-inflammatory T cell proliferation, therefore, limiting collateral tissue destruction. The aim of this study was to investigate whether ex vivo augmentation of human Tregs attenuates aneurysm formation in humanized murine model of AAA. Circulating Treg population in AAA patients and age- and gender-matched controls were determined by real-time polymerase chain reaction and flow cytometry. To create humanized murine model of AAA, irradiated Rag1-deficient (Rag1-/-) mice, without mature T lymphocytes, at 7 weeks of age were given 5 × 106 of human CD4+ T cells intraperitoneally. Then the mice underwent CaCl2 aneurysm induction. Aortic diameters were measured before and at 6 weeks after aneurysm induction. Aortic tissue was collected for histology and protein extraction. Verhoeff-Van Gieson stain was used for staining elastic fiber. CD4+ T cells in the aortic tissue were detected by immunohistochemical staining. In human peripheral blood mononuclear cells, the proportion of Tregs are decreased in AAA patients compared with matched control patients with significant vascular disease. We first validated the role of Tregs in the CaCl2 model of AAA. To determine the role of human T cells in AAA formation, Rag1-/- mice, resistant to CaCl2-aneurysm induction, were transplanted with human CD4+ T cells. Human CD4+ T cells were able to drive aneurysm formation in Rag1-/- mice. We show that ex vivo augmentation of human Tregs by interleukin-2 resulted in decreased aneurysm progression. These data suggest that the ex vivo expansion of human Tregs may be a potential therapeutic strategy for inhibiting progression of AAA.


Diffusion-weighted magnetic resonance imaging in symptomatic vertebrobasilar atherosclerosis and dissection.
Acute multiple brain infarction (AMBI) pattern on diffusion-weighted imaging (DWI) is associated with arterial and cardiac sources of embolism. The DWI characteristics of patients with stroke due to vertebrobasilar arterial dissection and atherosclerotic disease have not been reported in detail. To describe the DWI stroke patterns in patients with posterior circulation occlusive disease to determine mechanisms of ischemia. Retrospective analysis of infarct patterns in patients with symptomatic vertebrobasilar disease. Large community-based teaching hospital. Patients admitted with stroke due to vertebrobasilar disease were identified retrospectively. Patients were included if DWI was obtained within 7 days of symptom onset. Infarct patterns were analyzed according to established templates of vascular territories. Eleven patients with vertebral dissection and 39 patients with atherothrombosis were identified. An AMBI pattern was present in 8 (72%) of 11 patients with arterial dissections and 25 (64%) of 39 patients with atherosclerotic disease (P = .48). Distal embolism to the terminal branches of the basilar artery occurred with equal frequency in both groups and was found in half of all cases. Isolated thalamic infarction did not occur. Pontine infarction was noted in 2 (18%) of 11 patients with dissections and 18 (46%) of 39 patients with atherosclerosis (P = .09). Cerebellar border zone involvement was found in 14 (36%) of 39 patients with atherosclerosis and 4 (37%) of 11 patients with dissections (P = .6). Large arterial disease is frequently associated with AMBI in the posterior circulation. The incidence of AMBI was comparable to that reported in the anterior circulation. This DWI study supports the importance of embolism as the main mechanism of infarction in patients with vertebrobasilar occlusive disease. On the basis of our experience, large-vessel vertebrobasilar disease rarely causes isolated small-vessel thalamic infarction.


Sickness absence and disability pension following breast cancer - A population-based matched cohort study.
To compare sickness absence and disability pension in a population-based cohort of women with breast cancer (n = 463) from 1 year pre-diagnosis until 3 years post-diagnosis with a matched control group (n = 2310), and to investigate predictors of sickness absence during the 2nd and 3rd year post-diagnosis. Following breast cancer, the proportion of disease-free women with sickness absence decreased post-diagnosis (1st-3rd year; 78%-31%-19%), but did not reach the pre-diagnostic level (14%; P < 0.05). Post-diagnosis, patients were more likely than controls to be sickness absent (1st-3rd year; P < 0.001). No between-group differences were observed for disability pension post-diagnosis (P > 0.05). Among patients, chemotherapy, baseline fatigue and pre-diagnosis sick days predicted sickness absence during the 2nd, 3rd, and 2nd and 3rd year post-diagnosis, respectively (P < 0.05). Breast cancer is associated with increased sickness absence 3 years post-diagnosis. In a clinical setting, prevention and treatment of side effects are important in reducing long-term consequences.


How do elderly spouse care givers of people with Alzheimer disease experience the disclosure of dementia diagnosis and subsequent care?
To examine the experiences of spousal care givers of Alzheimer patients to disclosure of dementia diagnosis and subsequent care. A random sample of 1943 spousal care givers of people receiving medication for Alzheimer disease (AD) was sent a cross-sectional postal survey about their opinions on the disclosure of dementia and follow-up care. A smaller qualitative study (n = 63) included open-ended questions concerning their experiences of the same topics. The response rate for the survey was 77%. Of the respondents, 1214 of 1434 acknowledged themselves as their spouse's care giver. The mean age of the care givers was 78.2 years, and that of demented spouses, 80.5 years. Of the care givers, 63% were women. The couples had long-lasting marriages (mean 52 years). Of the care givers, 93% reported that dementia had been disclosed openly to their spouse; 97% also preferred that physicians openly inform the patients of the dementia diagnosis, although 55% of their spouses with AD had developed depressive symptoms after the disclosure. Of the care givers, 71% felt they had received sufficient information about dementia. However, only 50% estimated that their spouses' follow-up care had been well organised. The responses in the qualitative study indicated that many care givers felt grief and anxiety. They also expressed feelings of loneliness and uncertainty about how to deal with follow-up care for dementia. Elderly spousal care givers were quite satisfied with the information given them about dementia. However, the support with regard to the follow-up care of care-giving families failed to meet their needs adequately.


Evidence for Inbreeding and Genetic Differentiation among Geographic Populations of the Saprophytic Mushroom Trogia venenata from Southwestern China.
During the past 40 years, more than 400 Sudden Unexplained Deaths (SUDs) have occurred in Yunnan, southwestern China. Epidemiological and toxicological analyses suggested that a newly discovered mushroom called Trogia venenata was the leading culprit for SUDs. At present, relatively little is known about the genetics and natural history of this mushroom. In this study, we analyzed the sequence variation at four DNA fragments among 232 fruiting bodies of T. venenata collected from seven locations. Our ITS sequence analyses confirmed that all the isolates belonged to the same species. The widespread presence of sequence heterozygosity within many strains at each of three protein-coding genes suggested that the fruiting bodies were diploid, dikaryotic or heterokaryotic. Within individual geographic populations, we found significant deviations of genotype frequencies from Hardy-Weinberg expectations, with the overall observed heterozygosity lower than that expected under random mating, consistent with prevalent inbreeding within local populations. The geographic populations were overall genetically differentiated. Interestingly, while a positive correlation was found between population genetic distance and geographic distance, there was little correlation between genetic distance and barium concentration difference for the geographic populations. Our results suggest frequent inbreeding, geographic structuring, and limited gene flow among geographic populations of T. venenata from southwestern China.


Gender-specific differences in left ventricular remodelling in obesity: insights from cardiovascular magnetic resonance imaging.
As obesity-related cardiovascular mortality, although elevated when compared with normal weight, is lower in females than in males at every body mass index (BMI) level, we aimed to investigate gender-specific differences in left ventricular (LV) hypertrophy in obesity, which themselves have been shown to have varying prognostic value. In total, 741 subjects (female, n = 399) without identifiable cardiovascular risk factors (BMI 15.7-59.2 kg/m(2)) underwent cardiovascular magnetic resonance (1.5 T) to determine LV mass, end-diastolic volume (EDV, mL), and LV mass/volume ratio (LVM/VR). Across both sexes, there was a strong positive correlation between BMI and LV mass (male r = 0.44, female r = 0.57, both P < 0.001), with males showing a greater LV hypertrophic response (male +2.3 vs. female +1.6 g per BMI point increase, P = 0.001). Concentric hypertrophy was present in both sexes and LVM/VR positively correlated to BMI (male r = 0.45, female r = 0.29, both P < 0.001) on linear regression analysis. However, the degree of concentric hypertrophy was greater in males (male +0.13 vs. female +0.06 LVM/VR increase per BMI point increase, P = 0.001). On the other hand, females showed a greater LV cavity dilatory response (female +1.1 vs. male +0.3 mL per BMI point increase, P < 0.001). Indeed, in contrast to females, where BMI and LV-EDV were positively correlated (r = 0.38, P < 0.001), BMI did not correlate with EDV in men (r = 0.03, P = 0.62). In the absence of traditional cardiovascular risk factors, obese men show predominantly concentric hypertrophy, whereas obese women exhibit both eccentric and concentric hypertrophy. As concentric hypertrophy is more strongly related to cardiovascular mortality than eccentric hypertrophy, our observations may explain the observed gender difference in obesity-related mortality.


Systematic review of diet quality indices and their associations with health-related outcomes in children and adolescents.
Diet quality indices add an important dimension to dietary assessment. The aim of this systematic review was to: (i) identify and describe the attributes and applications of diet quality indices developed for use or used in paediatric populations; (ii) describe associations between these diet quality indices and health-related variables in paediatric populations; and (iii) identify factors that are associated with diet quality in paediatric populations worldwide. Studies were identified by searching electronic databases for relevant papers from 1980 to October 2013 using keywords. Inclusion criteria were original studies that utilised a quantitative measure of diet quality in children and adolescents aged 0-18 years. One hundred and nineteen studies met the inclusion criteria, from which 80 different diet quality indices were identified. The majority of studies had >1000 participants and were of acceptable quality. Of the 56 studies that investigated health-related outcomes, weight status was the most researched. Europe produced the most number of diet quality indices (n = 27 indices). Of the 119 studies, seven intervention studies were identified. Paediatric diet quality indices were found to be associated with environmental, behavioural and maternal factors. The use of diet quality indices in paediatric populations is a rapidly expanding area of research in diverse populations internationally. In economically disadvantaged countries, diet quality indices may be predictive of child growth. However, prospective cohort, intervention and validation studies are required to draw stronger conclusions concerning risk of future disease in paediatric populations in general.


Evaluation of the 3D fractal dimension as a marker of structural brain complexity in multiple-acquisition MRI.
Fractal analysis represents a promising new approach to structural neuroimaging data, yet systematic evaluation of the fractal dimension (FD) as a marker of structural brain complexity is scarce. Here we present in-depth methodological assessment of FD estimation in structural brain MRI. On the computational side, we show that spatial scale optimization can significantly improve FD estimation accuracy, as suggested by simulation studies with known FD values. For empirical evaluation, we analyzed two recent open-access neuroimaging data sets (MASSIVE and Midnight Scan Club), stratified by fundamental image characteristics including registration, sequence weighting, spatial resolution, segmentation procedures, tissue type, and image complexity. Deviation analyses showed high repeated-acquisition stability of the FD estimates across both data sets, with differential deviation susceptibility according to image characteristics. While less frequently studied in the literature, FD estimation in T2-weighted images yielded robust outcomes. Importantly, we observed a significant impact of image registration on absolute FD estimates. Applying different registration schemes, we found that unbalanced registration induced (a) repeated-measurement deviation clusters around the registration target, (b) strong bidirectional correlations among image analysis groups, and (c) spurious associations between the FD and an index of structural similarity, and these effects were strongly attenuated by reregistration in both data sets. Indeed, differences in FD between scans did not simply track differences in structure per se, suggesting that structural complexity and structural similarity represent distinct aspects of structural brain MRI. In conclusion, scale optimization can improve FD estimation accuracy, and empirical FD estimates are reliable yet sensitive to image characteristics.


Effect of age and monosodium-L-glutamate (MSG) treatment on neurotransmitter content in brain regions from male Fischer-344 rats.
Peripheral administration of monosodium-L-glutamate (MSG) has been found to be neurotoxic in neonatal rats. When administered in an acute, subconvulsive dose (500 mg/kg i.p.), MSG altered neurotransmitter content in discrete brain regions of adult (6 month old) and aged (24 month old) male Fischer-344 rats. Norepinephrine (NE) content was reduced in both the hypothalamus (16%) and cerebellum (11%) of adult rats, but was increased in both the hypothalamus (7%) and cerebellum (14%) of aged rats after MSG treatment. MSG also altered the dopamine content in adult rats in both the posterior cortex and the striatum, causing a reduction (23%) and an increase (12%), respectively. Glycine content in the midbrain of aged rats increased (21%) after MSG injection. Of particular interest is the widespread monoamine and amino acid deficits found in the aged rats in many of the brain regions examined. NE content was decreased (11%) in the cerebellum of aged rats. Dopamine content was reduced in both the posterior cortex (35%) and striatum (10%) of aged rats compared to adult animals. Cortical serotonergic deficits were present in aged rats with reductions in both the frontal (13%) and posterior cortex (21%). Aged rats also displayed deficits in amino acids, particularly the excitatory amino acids. There were glutamate deficits (9-18% reductions) in the cortical regions (posterior and frontal) as well as midbrain and brain stem. Aspartate, the other excitatory amino acid transmitter, was reduced 10% in the brainstem of aged rats. These data indicate that an acute, subconvulsive, dose of MSG may elicit neurochemical changes in both adult and aged male Fisher-344 rats, and that there are inherent age-related deficits in particular neurotransmitters in aged male Fisher-344 rats as indicated by the reductions in both monoamines and amino acids.


Oxolinic Acid Binding at Goethite and Akaganéite Surfaces: Experimental Study and Modeling.
Oxolinic acid (OA) is a widely used quinolone antibiotic in aquaculture. In this study, its interactions with synthetic goethite (α-FeOOH) and akaganéite (β-FeOOH) particle surfaces were monitored to understand the potential fate of OA in marine sediments where these phases occur. Batch sorption experiments, liquid chromatography (LC) analyses of supernatants, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and multisite complexation (MUSIC) modeling were used to monitor OA binding at these particle surfaces. Both LC and ATR-FTIR showed that adsorption did not degrade OA, and that OA adsorption was largely unaffected by NaCl concentrations (10-1000 mM). This was explained further by ATR-FTIR suggesting the formation of metal-bonded complexes at circumneutral to low pHc = -log [H(+)] and with a strongly hydrogen-bonded complex at high pHc. The stronger OA binding to akaganéite can be explained both by the higher isoelectric point/point-of-zero charge (9.6-10) of this mineral than of goethite (9.1-9.4), and an additional OA surface complexation mechanism at the (010) plane. Geminal sites (≡Fe(OH2)2(+)) at this plane could be especially reactive for metal-bonded complexes, as they facilitate a mononuclear six-membered chelate complex via the displacement of two hydroxo/aquo groups at the equatorial plane of a single Fe octahedron. Collectively, these findings revealed that Fe-oxyhydroxides may strongly contribute to the fate and transport of OA-type antibacterial agents in marine sediments and waters.


Living with chronic illness in adults: a concept analysis.
To report an analysis of the concept of Living with chronic illness in adults, using Rodger's evolutionary analytical methodology. In the literature, several qualitative studies exist that address the question of Living with chronic illness from the adult patient's perspective. However, the lack of clarity and consensus among the existing studies renders this concept ambiguous when it is analysed in depth. A narrative review. A systematic search has been carried out on electronic databases such as Medline (PubMed), Cinahl (Ebsco), Cochrane Library, PsycINFO (Ovid), Embase, Cuiden, Dialnet and Scielo. This was limited to articles published in either Spanish or English, from 2003-2013. Living with chronic illness is a complex, dynamic, cyclic and multidimensional process, and involves the development of five different attributes: Acceptance, Coping, Self-management, Integration and Adjustment. Depending on how these attributes operate, there are four different ways of living which can result from the process of Living with chronic illness: (1) Disavowal, (2) False Normality, (3) The New Normal and (4) Disruption. This paper contributes to the understanding of the concept 'Living with chronic illness'. Findings in this analysis have to be evaluated with caution and further research is needed on this topic to confirm them. Also, more studies in evaluating how patients live a long-term condition are recommended to foster patient-centred care. Findings generated from this concept analysis can raise awareness of Living with chronic illness so that this process could be assessed in a correct and uniform way in the clinical community and improved when needed.