The Role of Ego Networks in Compulsive Exercise Behavior Among a Sample of College Sorority Women.
Compulsive exercise (CE) is a harmful form of exercise that elevates the risk of developing/sustaining clinical eating disorders. College-aged sorority women are especially prone to CE. Due to the pronounced impact social relationships have on college students' behavior, this study aims to examine personal networks and CE among a sample of sorority women through an egocentric network analysis. A total of 204 women in a sorority from a large, private university in the southeastern United States completed a cross-sectional survey in spring 2015. Descriptive and regression analyses were conducted on demographic, attribute, and ego network data. Relationships with siblings, significant others, and roommates were protective against CE in this sample. Conversely, body dissatisfaction and exercise frequency predicted CE. Findings suggest that social relationships can impact CE behaviors in this sample. Along with promoting body satisfaction and healthy exercise, public health efforts should focus on facilitating close interpersonal relationships, especially between sorority women and siblings, significant others, and roommates.


Autoantibodies in childhood opsoclonus-myoclonus syndrome.
Opsoclonus-myoclonus syndrome or Dancing Eye Syndrome (OMS/DES) is a rare neurological disorder of children, which associates with neuroblastoma (NB) in approximately 50% of cases. We examined sera from five patients with (OMS-NB(+)) and five without NB (OMS-NB(-)) for autoantibodies. OMS-NB(-) IgG bound to the surface of a NB cell line, whereas IgG from OMS-NB(+) and from NB patients without OMS/DES bound only to permeabilised cells. Both OMS-NB(+) and OMS-NB(-) reduced proliferation of NB cells. We also present a case report of a child with OMS/DES without NB who made a complete recovery without treatment. Serum antibodies at presentation bound to the surface and decreased NB cell proliferation but had decreased 9 weeks later when the child was asymptomatic. These results demonstrate that sera from some OMS/DES patients contain IgG antibodies that are potentially pathogenic.


Retraction to: Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health.
After becoming aware that the study in the above-referenced article did not fully account for certain information in the Population Assessment of Tobacco and Health [PATH] Wave 1 survey, the editors of Journal of the American Heart Association reviewed the peer review process. During peer review, the reviewers identified the important question of whether the myocardial infarctions occurred before or after the respondents initiated e-cigarette use, and requested that the authors use additional data in the PATH codebook (age of first MI and age of first e-cigarettes use) to address this concern. While the authors did provide some additional analysis, the reviewers and editors did not confirm that the authors had both understood and complied with the request prior to acceptance of the article for publication. Post publication, the editors requested Dr. Bhatta et al conduct the analysis based on when specific respondents started using e-cigarettes, which required ongoing access to the restricted use dataset from the PATH Wave 1 survey.1 The authors agreed to comply with the editors' request. The deadline set by the editors for completion of the revised analysis was not met because the authors are currently unable to access the PATH database. Given these issues, the editors are concerned that the study conclusion is unreliable. The editors hereby retract the article from publication in Journal of the American Heart Association. [original article URL: https://www.ahajournals.org/doi/10.1161/JAHA.119.012317] Reference 1. Bhatta DN, Glantz SA. Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health. J Am Heart Assoc. 2019;8:e012317. DOI: 10.1161/JAHA.119.012317.


Complementary frequency shifter based on polarization modulator used for generation of a high-quality frequency-locked multicarrier.
A novel polarization-modulator-based complementary frequency shifter (PCFS) has been proposed and then used to implement the generation of a frequency-locked multicarrier with single- and dual-recirculating frequency shifting loops, respectively. The transfer functions and output properties of PCFS and PCFS-based multicarrier generator have been studied theoretically. Based on our simulation results through VPItransmissionMaker software, 100 stable carriers have been obtained with acceptable flatness while no DC bias control is required. The results show that the proposed PCFS has the potential to become a commercial product and then used in various scenarios.


The influence of climate on the timing and rate of spring bird migration.
Ecological processes are changing in response to climatic warming. Birds, in particular, have been documented to arrive and breed earlier in spring and this has been attributed to elevated spring temperatures. It is not clear, however, how long-distance migratory birds that overwinter thousands of kilometers to the south in the tropics cue into changes in temperature or plant phenology on northern breeding areas. We explored the relationships between the timing and rate of spring migration of long-distance migratory birds, and variables such as temperature, the North Atlantic Oscillation (NAO) and plant phenology, using mist net capture data from three ringing stations in North America over a 40-year period. Mean April/May temperatures in eastern North America varied over a 5 degrees C range, but with no significant trend during this period. Similarly, we found few significant trends toward earlier median capture dates of birds. Median capture dates were not related to the NAO, but were inversely correlated to spring temperatures for almost all species. For every 1 degrees C increase in spring temperature, median capture dates of migratory birds averaged, across species, one day earlier. Lilac (Syringa vulgaris) budburst, however, averaged 3 days earlier for every 1 degrees C increase in spring temperature, suggesting that the impact of temperature on plant phenology is three times greater than on bird phenology. To address whether migratory birds adjust their rate of northward migration to changes in temperature, we compared median capture dates for 15 species between a ringing station on the Gulf Coast of Louisiana in the southern USA with two stations approximately 2,500 km to the north. The interval between median capture dates in Louisiana and at the other two ringing stations was inversely correlated with temperature, with an average interval of 22 days, that decreased by 0.8 days per 1 degrees C increase in temperature. Our results suggest that, although the onset of migration may be determined endogenously, the timing of migration is flexible and can be adjusted in response to variation in weather and/or phenology along migration routes.


Use of Esophageal Hemoximetry to Assess the Effect of Packed Red Blood Cell Transfusion on Gastrointestinal Oxygenation in Newborn Infants.
Objectives There are no widely accepted methods of continuously monitoring gut oxygenation in the newborn during packed red blood cell transfusion. We investigated the use of an orally inserted light spectroscopy probe to measure lower esophageal oxyhemoglobin saturations (eStO2) before, during, and after transfusion and made comparisons with abdominal near-infrared spectroscopy (NIRS) and superior mesenteric artery (SMA) flow. Study Design Thirteen neonates with corrected gestational ages ranging from 22 weeks, 0 day to 37 weeks, 5 days were enrolled. eStO2 and NIRS measurements were recorded continuously for a 25-hour period starting 1 hour prior to starting the 4-hour transfusion. Transabdominal ultrasound was used to measure SMA flow prior to, upon completion, and 20 hours after the transfusion. Results Twelve infants completed the study. eStO2 was well-tolerated and was weakly (r = 0.06) correlated (p < 0.001) with NIRS. Compared with NIRS, eStO2 demonstrated a markedly greater variation in oxyhemoglobin values. NIRS and SMA flow measurements did not change, while eStO2 increased from 48 ± 5% and 45 ± 5% in the pre- and intratransfusion periods to 57 ± 4% in the posttransfusion period (p = 0.03). Conclusion Measurement of eStO2 is feasible in neonates and may provide a continuous and sensitive index of rapid changes in mesenteric oxygenation in this patient population.


Techniques for immediate core buildup of endodontically treated teeth.
Access to the pulp chamber for endodontic treatment is indicated inter alia as a result of extensive caries, trauma to the tooth causing fracture or loss of vitality, requiring restoration of the missing tooth structure. Different approaches and materials are described in the literature for foundation restorations, either with a cast post and core or immediately, with a chairside post-and-core system. This article briefly reviews the current data regarding the microbiologic, prosthetic, mechanical, and periodontal aspects while emphasizing the immediate approach using amalgam, resin composites, and glass ionomers. Factors affecting retention of the post are presented to guide the clinician in selecting a suitable post-and-core system to preserve optimal root structure and prevent root fracture. Three clinical cases are presented in which tooth structure was restored using different techniques: in the first two, provisional acrylic resin shells, one custom made and the other prefabricated, were used to house an amalgam coronal-radicular dowel core, where in the third case, a copper band was used for a composite post-and-core system. All cases emphasize the ease of production and short chairtime in the stages of crown fabrication.


Meta-analysis of individual patient data versus aggregate data from longitudinal clinical trials.
In clinical trials following individuals over a period of time, the same assessment may be made at a number of time points during the course of the trial. Our review of current practice for handling longitudinal data in Cochrane systematic reviews shows that the most frequently used approach is to ignore the correlation between repeated observations and to conduct separate meta-analyses at each of a number of time points. The purpose of this paper is to show the link between repeated measurement models used with aggregate data and those used when individual patient data (IPD) are available, and provide guidance on the methods that practitioners might use for aggregate data meta-analyses, depending on the type of data available. We discuss models for the meta-analysis of longitudinal continuous outcome data when IPD are available. In these models time is included either as a factor or as a continuous variable, and account is taken of the correlation between repeated observations. The meta-analysis of IPD can be conducted using either a one-step or a two-step approach: the latter involves analysing the IPD separately in each study and then combining the study estimates taking into account their covariance structure. We discuss the link between models for use with aggregate data and the two-step IPD approach, and the problems which arise when only aggregate data are available. The methods are applied to IPD from 5 trials in Alzheimer's disease. Two major issues for the meta-analysis of aggregate data are the lack of information about correlation coefficients and the effect of missing data at the patient-level. Application to the Alzheimer's disease data set shows that ignoring correlation can lead to different pooled estimates of the treatment difference and their standard errors. Furthermore, the amount of missing data at the patient level can affect these estimates. The models assume fixed treatment effects across studies, and that any missing data is missing at random, both at the patient-level and the study level. It is preferable to obtain IPD from all studies to correctly account for the correlation between repeated observations. When IPD are not available, the ideal aggregate data are model-based estimates of treatment difference and their variance and covariance estimates. If covariance estimates are not available, sensitivity analyses should be undertaken to investigate the robustness of the results to different amounts of correlation.


Rutin attenuates gentamicin-induced renal damage by reducing oxidative stress, inflammation, apoptosis, and autophagy in rats.
Gentamicin is commonly used against gram-negative microorganisms. Its therapeutic use is mainly limited by nephrotoxicity. This study was aimed at evaluating the effect of rutin on oxidative stress, inflammation, apoptosis, and autophagy in gentamicin-induced nephrotoxicity in rats. The rats were treated with saline intraperitoneally (group I), 150 mg/kg of rutin orally (group II), 80 mg/kg of gentamicin intraperitoneally for 8 d (group III), or 150 mg/kg of rutin plus 80 mg/kg of gentamicin (group IV). The serum urea, creatinine, kidney malondialdehyde (MDA), and reduced glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and protein concentration were measured, and renal histopathology analysis and immunohistochemical staining were performed. Rutin pretreatment attenuated nephrotoxicity induced by gentamicin by reducing the urea, creatinine, and MDA levels and increasing the SOD, CAT, and GPx activity, and the GSH levels. The rutin also inhibited inducible nitric oxide synthase (iNOS), cleaved caspase-3 and light chain 3B (LC3B), as evidenced by immunohistochemical staining. The present study demonstrates that rutin exhibits antioxidant, anti-inflammatory, anti-apoptotic, and anti-autophagic effects and that it attenuates gentamicin-induced nephrotoxicity in rats.


Social workers as disaster responders during the COVID-19 pandemic: Polish experience.
This article aims to present the experiences of 284 social workers as disaster responders during the Covid-19 pandemic-the study conducted among social workers from public social assistance institutions in the Greater Poland Province, Poland.During the pandemic, the vast majority of social workers carried out administrative activities consisting of qualifying people to receive social assistance benefits. The activities that were undertaken the least frequently during the pandemic were: initiating new forms of assistance, developing social welfare programs acting as an advocate for the rights and interests of clients. Respondents observed changes in the functioning of social assistance institutions during the pandemic on several levels: guarantying access to personal protective equipment, changes in the way of working, lack of protecting the mental health of workers. The respondents were asked to rate on cooperation with the environment to mitigate the effects of the pandemic. Cooperation with institutions such as police, non-governmental organizations, informal groups, and the Wielkopolska Province Office in Poznan was rated the highest. The results of the present study demonstrate that social workers are essential disaster responders to the COVID-19 pandemic. The majority of polish social workers did not lose touch with the local environment and, risking their own health, undertook activities for people and families in need.


The skilled attendance index: proposal for a new measure of skilled attendance at delivery.
Increasing the proportion of deliveries with skilled attendance is widely regarded as key to reducing maternal mortality and morbidity in developing countries. The percentage of deliveries with a health professional is commonly used to assess skilled attendance, but measures only the presence of an attendant, not the skills used or the enabling environment To supplement currently available information on the presence of an attendant at delivery, a method to measure the extent of skilled attendance at delivery through use of clinical records was devised. Data were collected from 416 delivery records in hospitals, government health centres and private non-hospital maternity facilities servicing Kintampo District, Ghana, using a case extraction form. Based on the defined criteria, summary measures of skilled attendance were calculated. Between 32.6% and 93.0% of the criteria for skilled attendance were met in the sample, with a mean of 65.5%. No delivery met all the criteria. A Skilled Attendance Index (SAI) was developed as a composite measure of delivery care. The SAI revealed that 26.9% of delivery records met at least three-quarters of the criteria for skilled attendance. Documentation of haemoglobin, current pregnancy complications, post-partum vital signs and completed partographs were amongst the criteria most poorly recorded. The purpose of applying these measures should be seen not as an end in itself but to advance improvements in delivery care.


Antibacterial efficacy of R-type pyocins towards Pseudomonas aeruginosa in a murine peritonitis model.
R-type pyocins are high-molecular-weight bacteriocins carried within the chromosomes of some bacterial species, such as Pseudomonas aeruginosa, and almost certainly evolved from lysogenic bacteriophages of the Myoviridae family. They contain no head structures and no DNA and are used as defense systems, usually against other strains of the same bacterial species. They bind with their tail fibers to targeted bacterial surface molecules and then kill by inserting a core or needle that dissipates the bacterial membrane potential. Their mechanism of action, high bactericidal potency (one pyocin particle can kill one bacterium), and focused spectrum suggest that R-type pyocins could be developed as antibacterial agents. In a lethal mouse peritonitis model, submicrogram quantities of pyocin prevent death from 90% lethal dose inocula of a pyocin-sensitive, clinical isolate of P. aeruginosa. We show here the dose response curves, treatment windows, or periods of response after infection and the several-log-unit acute reduction of bacterial load in blood and spleen samples, suggesting that R-type pyocins have several characteristics that one would expect from an effective therapeutic.


Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders.
Until recently it was believed that no more than 1% of the general population has bipolar disorder. Emerging transatlantic data are beginning to provide converging evidence for a higher prevalence of up to at least 5%. Manic states, even those with mood-incongruent features, as well as mixed (dysphoric) mania, are now formally included in both ICD-10 and DSM-IV. Mixed states occur in an average of 40% of bipolar patients over a lifetime; current evidence supports a broader definition of mixed states consisting of full-blown mania with two or more concomitant depressive symptoms. The largest increase in prevalence rates, however, is accounted for by 'softer' clinical expressions of bipolarity situated between the extremes of full-blown bipolar disorder where the person has at least one manic episode (bipolar I) and strictly defined unipolar major depressive disorder without personal or family history for excited periods. Bipolar II is the prototype for these intermediary conditions with major depressions and history of spontaneous hypomanic episodes; current evidence indicates that most hypomanias pursue a recurrent course and that their usual duration is 1-3 days, falling below the arbitrary 4-day cutoff required in DSM-IV. Depressions with antidepressant-associated hypomania (sometimes referred to as bipolar III) also appear, on the basis of extensive international research neglected by both ICD-10 and DSM-IV, to belong to the clinical spectrum of bipolar disorders. Broadly defined, the bipolar spectrum in studies conducted during the last decade accounts for 30-55% of all major depressions. Rapid-cycling, defined as alternation of depressive and excited (at least four per year), more often arise from a bipolar II than a bipolar I baseline; such cycling does not in the main appear to be a distinct clinical subtype - but rather a transient complication in 20% in the long-term course of bipolar disorder. Major depressions superimposed on cyclothymic oscillations represent a more severe variant of bipolar II, often mistaken for borderline or other personality disorders in the dramatic cluster. Moreover, atypical depressive features with reversed vegetative signs, anxiety states, as well as alcohol and substance abuse comorbidity, is common in these and other bipolar patients. The proper recognition of the entire clinical spectrum of bipolarity behind such 'masks' has important implications for psychiatric research and practice. Conditions which require further investigation include: (1) major depressive episodes where hyperthymic traits - lifelong hypomanic features without discrete hypomanic episodes - dominate the intermorbid or premorbid phases; and (2) depressive mixed states consisting of few hypomanic symptoms (i.e., racing thoughts, sexual arousal) during full-blown major depressive episodes - included in Kraepelin's schema of mixed states, but excluded by DSM-IV. These do not exhaust all potential diagnostic entities for possible inclusion in the clinical spectrum of bipolar disorders: the present review did not consider cyclic, seasonal, irritable-dysphoric or otherwise impulse-ridden, intermittently explosive or agitated psychiatric conditions for which the bipolar connection is less established. The concept of bipolar spectrum as used herein denotes overlapping clinical expressions, without necessarily implying underlying genetic homogeneity. In the course of the illness of the same patient, one often observes the varied manifestations described above - whether they be formal diagnostic categories or those which have remained outside the official nosology. Some form of life charting of illness with colored graphic representation of episodes, stressors, and treatments received can be used to document the uniquely varied course characteristic of each patient, thereby greatly enhancing clinical evaluation.


A hierarchical competing systems model of the emergence and early development of executive function.
The hierarchical competing systems model (HCSM) provides a framework for understanding the emergence and early development of executive function--the cognitive processes underlying the conscious control of behavior--in the context of search for hidden objects. According to this model, behavior is determined by the joint influence of a developmentally invariant habit system and a conscious representational system that becomes increasingly influential as children develop. This article describes a computational formalization of the HCSM, reviews behavioral and computational research consistent with the model, and suggests directions for future research on the development of executive function.


Planning and self-efficacy interventions encouraging replacing energy-dense foods intake with fruit and vegetable: A longitudinal experimental study.
This longitudinal experimental study compared effects of self-efficacy, planning and education-based conditions, encouraging adolescents to eat fruit and vegetable in place of energy-dense foods. Data were collected among 506 adolescents (13-18 years old) who were randomly assigned to control (n = 181), planning (n = 153) or self-efficacy (n = 172) conditions. Measurements were taken at baseline (T1), at a 2-month follow-up (T2), and at a 14-month follow-up (T3). Interventions/control group procedures were delivered at T1 and T2. Self-reports of fruit and vegetable intake (FVI) and energy-dense foods intake were collected at three times. Cognitive mediators (self-efficacy and planning) were assessed at T1 and T2. Body weight and height were objectively measured at T1 and T3. Similar significant increases of FVI were found for planning and self-efficacy interventions (T3). The planning intervention did not influence energy-dense food intake (T3), but the self-efficacy intervention tended to result in stabilising intake (compared to an increase found in the control group). There were no effects on body weight. Similar patterns were found for the total sample and for a subsample of adolescents with overweight/obesity. The effects of interventions on FVI were mediated by respective cognitions.


RNA-seq and microarray complement each other in transcriptome profiling.
RNA-seq and microarray are the two popular methods employed for genome-wide transcriptome profiling. Current comparison studies have shown that transcriptome quantified by these two methods correlated well. However, none of them have addressed if they complement each other, considering the strengths and the limitations inherent with them. The pivotal requirement to address this question is the knowledge of a well known data set. In this regard, HrpX regulome from pathogenic bacteria serves as an ideal choice as the target genes of HrpX transcription factor are well studied due to their central role in pathogenicity. We compared the performance of RNA-seq and microarray in their ability to detect known HrpX target genes by profiling the transcriptome from the wild-type and the hrpX mutant strains of γ-Proteobacterium Xanthomonas citri subsp. citri. Our comparative analysis indicated that gene expression levels quantified by RNA-seq and microarray well-correlated both at absolute as well as relative levels (Spearman correlation-coefficient, rs > 0.76). Further, the expression levels quantified by RNA-seq and microarray for the significantly differentially expressed genes (DEGs) also well-correlated with qRT-PCR based quantification (rs = 0.58 to 0.94). Finally, in addition to the 55 newly identified DEGs, 72% of the already known HrpX target genes were detected by both RNA-seq and microarray, while, the remaining 28% could only be detected by either one of the methods. This study has significantly advanced our understanding of the regulome of the critical transcriptional factor HrpX. RNA-seq and microarray together provide a more comprehensive picture of HrpX regulome by uniquely identifying new DEGs. Our study demonstrated that RNA-seq and microarray complement each other in transcriptome profiling.


Response to "CAR T-Cell Therapy: Updates in Nursing Management".
I have found Clinical Journal of Oncology Nursing (CJON) articles to be enlightening and well written, and I look forward to reading CJON monthly to expand my general cancer care knowledge. I have been a blood and marrow transplantation (BMT) nurse since 1976; our BMT program birthed the chimeric antigen receptor (CAR) T-cell program. In October 2020, I retired as a BMT supervisor and policy keeper from the Seattle Cancer Care Alliance (SCCA), so I am very familiar with both specialties. I was lucky to spend my career at the Fred Hutchinson Cancer Research Center (FHCRC), which has emphasized research at its core. Clinical nutrition research has been a mainstay since the beginning of the program.


Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin-10.
Interleukin-12 (IL-12) induces differentiation of T helper 1 (Th1) cells, primarily through its ability to prime T cells for high interferon-gamma (IFN-gamma) production. We now report that the presence of IL-12 during the first several days of in vitro clonal expansion in limiting dilution cultures of polyclonally stimulated human peripheral blood CD4+ and CD8+ T cells also induces stable priming for high IL-10 production. This effect was demonstrated with T cells from both healthy donors and HIV+ patients. Priming for IL-4 production, which requires IL-4, was maximum in cultures containing both IL-12 and IL-4. IL-4 modestly inhibited the IL-12-induced priming for IFN-gamma, but almost completely suppressed the priming for IL-10 production. A proportion of the clones generated from memory CD45RO+ cells, but not those generated from naive CD45RO- CD4+ T cells, produced some combinations of IFN-gamma, IL-10, and IL-4 even in the absence of IL-12 and IL-4, suggesting in vivo cytokine priming; virtually all CD4+ clones generated from either CD45RO(-) or (+) cells, however, produced high levels of both IFN-gamma and IL-10 when IL-12 was present during expansion. These results indicate that each Th1-type (IFN-gamma) and Th2-type (IL-4 and IL-10) cytokine gene is independently regulated in human T cells and that the dichotomy between T cells with the cytokine production pattern of Th1 and Th2 cells is not due to a direct differentiation-inducing effect of immunoregulatory cytokines, but rather to secondary selective mechanisms. Particular combinations of cytokines induce a predominant generation of T cell clones with anomalous patterns of cytokine production (e.g., IFN-gamma and IL-4 or IFN-gamma and IL-10) that can also be found in a proportion of fresh peripheral blood T cells with "memory" phenotype or clones generated from them and that may identify novel Th subsets with immunoregulatory functions.


Musculoskeletal disorders among full-time homemakers in poor communities.
To examine factors associated with self-reported musculoskeletal disorders (MSD) among full-time female homemakers. Data on socio-demographic characteristics, lifestyle and health were collected on 1266 married women aged 15-59 years living in poor suburbs in the outskirts of Beirut, Lebanon. Independent associations with MSD of factors and characteristics were examined using odds ratios (ORs) derived from multiple logistic regression. Women's age, weight, and number of children were significantly, positively, independently associated with self-reported MSD, while women's conduct of specific household tasks were not. Women with MSD were more likely to be stressed than women without MSD (OR = 1.5). A major finding of this study was the positive association between distress and musculoskeletal disorders. The measures used to assess women's involvement in housework did not account for the duration of time spent performing each household task. Better measures of domestic labor, including housework and childcare, are required to understand better their impact on the health of full-time homemakers and on MSD in particular. Intervention programs to alleviate MSD in full-time homemakers should address psychosocial factors.


Lead-time in the European Randomised Study of Screening for Prostate Cancer.
Lead-time is defined as the time by which screening advances the diagnosis compared with absence of screening. A sufficiently long lead-time needs to be achieved so that cancer can be detected while still curable. A very short lead-time may indicate poor sensitivity of the screening test, while a very long lead-time suggests overdiagnosis. In the first screening round, a total of 56,294 men aged 55-74 years were screened with serum prostate specific antigen (PSA) in five countries of the European Randomised Study of Screening for Prostate Cancer (ERSPC) with an overall detection rate (prevalence) of 2.8% (1972 prostate cancers). Prostate cancer incidence among 92,142 men randomly allocated to the control arm of the trial was also assessed. Lead-time was estimated as the time required to accumulate a similar cumulative risk of prostate cancer in the control arm to the detection rate in the intervention arm, i.e. from the ratio of detection rate (prevalence of screen-detected cases) and expected incidence (cumulative risk). Using a serum PSA cut-off of 4 ng/ml, the mean lead-time in the whole study population was estimated as 6.8 years (95% confidence interval (95% CI) 7.9-8.4). It was 8 years in The Netherlands, 6 in Sweden and Finland, 5 in Italy and 4 in Belgium. The mean lead-time was similar, 6-7 years, at ages 50-64 years, but close to 8 years among men aged 65-74 years. A lower PSA cut-off level of 3 ng/ml used in Sweden and The Netherlands prolonged the mean lead-time by approximately 1 year. Lead-time based on advanced prostate cancer only was slightly shorter, mean 5.3 years (95% CI 4.6-6.0). The lead-time for the second screening round was slightly shorter than that for the first (5.9, 95% CI 5.4-6.4), reflecting a similar relation between detection rate and control group incidence. The lead-time for prostate cancer found in ERSPC substantially exceeded that found for breast, cervical and colorectal cancer screening. One round of prostate cancer screening can advance clinical diagnosis by 4-8 years. Overdiagnosis or detection of non-progressive tumours may contribute substantially to the lead-time.


Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis.
To determine whether Medicare's decision to cover routine administration of erythropoietin stimulating agents (ESAs) to treat anemia of end-stage renal disease (ESRD) has been a cost-effective policy relative to standard of care at the time. The authors used summary statistics from the actual cohort of ESRD patients receiving ESAs between 1995 and 2004 to create a simulated patient cohort, which was compared with a comparable simulated cohort assumed to rely solely on blood transfusions. Outcomes modeled from the Medicare perspective included estimated treatment costs, life-years gained, and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated relative to the hypothetical reference case of no ESA use in the transfusion cohort. Sensitivity of the results to model assumptions was tested using one-way and probabilistic sensitivity analyses. Estimated total costs incurred by the ESRD population were $155.47B for the cohort receiving ESAs and $155.22B for the cohort receiving routine blood transfusions. Estimated QALYs were 2.56M and 2.29M, respectively, for the two groups. The ICER of ESAs compared to routine blood transfusions was estimated as $873 per QALY gained. The model was sensitive to a number of parameters according to one-way and probabilistic sensitivity analyses. This model was counter-factual as the actual comparison group, whose anemia was managed via transfusion and iron supplements, rapidly disappeared following introduction of ESAs. In addition, a large number of model parameters were obtained from observational studies due to the lack of randomized trial evidence in the literature. This study indicates that Medicare's coverage of ESAs appears to have been cost effective based on commonly accepted levels of willingness-to-pay. The ESRD population achieved substantial clinical benefit at a reasonable cost to society.


Identification of leptomeningeal metastasis-related proteins in cerebrospinal fluid of patients with breast cancer by a combination of MALDI-TOF, MALDI-FTICR and nanoLC-FTICR MS.
Leptomeningeal metastasis (LM) is a devastating complication occurring in 5% of breast cancer patients. However, the current 'gold standard' of diagnosis, namely microscopic examination of the cerebrospinal fluid (CSF), is false-negative in 25% of patients at the first lumbar puncture. In a previous study, we analyzed a set of 151 CSF samples (tryptic digests) by MALDI-TOF and detected peptide masses that were differentially expressed in breast cancer patients with LM. In the present study, we obtain for a limited number of samples exact masses for these peptides by MALDI-FTICR MS measurements. Identification of these peptides was performed by electrospray FTICR MS after separation by nano-scale LC. The database results were confirmed by targeted high mass accuracy measurements of the fragment ions in the FTICR cell. The combination of automated high-throughput MALDI-TOF measurements and analysis by FTICR MS leads to the identification of 17 peptides corresponding to 9 proteins. These include proteins that are operative in host-disease interaction, inflammation and immune defense (serotransferrin, alpha 1-antichymotrypsin, hemopexin, haptoglobin and transthyretin). Several of these proteins have been mentioned in the literature in relation to cancer. The identified proteins alpha1-antichymotrypsin and apolipoprotein E have been described in relation to Alzheimer's disease and brain cancer.


Physical impairment and functional outcome in patients having lower extremity fractures after age 65.
The purpose of this study was to evaluate physical impairment and functional outcome in a group of patients who had a fracture of a lower extremity after age 65. The 30 subjects participating were treated between January 1992 and February 1998, for a unilateral fracture of the lower extremity. At the return examination, the patients' lower extremities were evaluated for range of motion (ROM) and strength. The participants also completed the Short Form 36 (SF-36) questionnaire, and their scores were compared with those of age-matched controls to determine relative disability. There were no statistically significant differences in ROM or muscle strength of the injured versus noninjured extremities, except in the case of knee flexion. The Mental Component Score (MCS) of the SF-36 in our study population was statistically different from that of controls, and there was no statistical difference in the Physical Component Score (PCS). A moderate correlation was found between the PCS and physical impairment.


Antioxidant potential of essential oil from Lavandula angustifolia in in vitro and ex vivo cultured liver cells.
Lavender is a commonly used herb in traditional medicine in Asia and Europe. It has been reported to be an effective medical plant in treating inflammation, depression and stress, thanks to its sedative and anxiolytic action, thrombotic, and antimicrobial properties. In the present study we investigated the protective effects of essential oil from Lavandula angustifolia (LO) against hydrogen peroxide and tert-butyl hydroperoxide -induced DNA damage. Also the effects of LO on the levels of enzymatic and non-enzymatic antioxidants (SOD-superoxide dismutase, GPx-glutathione peroxidase, GSH-glutathione) were evaluated in in vitro (human hepatoma cell line HepG2) and in ex vivo (freshly isolated rat hepatocytes) systems. The results showed that the oxidant-induced DNA lesions were significantly reduced in both systems pre-treated with the Lavandula angustifolia. The observed DNA-protective activity could be explained by both elevation of GPx activity in cells pre-treated with LO and antioxidant activity of LO.


Articular cartilage and labral lesions of the glenohumeral joint: diagnostic performance of 3D water-excitation true FISP MR arthrography.
To evaluate the diagnostic performance of MR arthrography in the detection of articular cartilage and labral lesions of the glenohumeral joint using a transverse 3D water-excitation true fast imaging with steady-state precession (FISP) sequence. Seventy-five shoulders were included retrospectively. Shoulder arthroscopy was performed within 6 months of MR arthrography. MR images were evaluated separately by two radiologists. They were blinded to clinical and arthroscopic information. Arthroscopy served as the reference standard. For the detection of humeral cartilage lesions, sensitivities and specificities were 86% (12/14)/89% (50/56) for observer 1 and 93%/86% for observer 2) for the transverse true FISP sequence and 64%/86% (50%/82% for observer 2) for the coronal intermediate-weighted spin-echo images. The corresponding values for the glenoidal cartilage were 60% (6/10)/88% (51/58) (80%/76% for observer 2) and 70%/86% (60%/74% for observer 2) respectively. For the detection of abnormalities of the anterior labrum (only assessed on true FISP images) the values were 94% (15/16)/84% (36/43) (88%/79% for observer 2). The corresponding values for the posterior labrum were 67% (8/12)/77% (36/47) (observer 2: 25%/74%). The kappa values for the grading of the humeral and glenoidal cartilage lesions were 0.81 and 0.55 for true FISP images compared with 0.49 and 0.43 for intermediate-weighted fast spin-echo images. Kappa values for true FISP evaluation of the anterior and posterior part of the labrum were 0.81 and 0.70. Transverse 3D true FISP MR arthrography images are useful for the difficult diagnosis of glenohumeral cartilage lesions and suitable for detecting labral abnormalities.


Awake Prone Positioning in Nonintubated Patients With Acute Hypoxemic Respiratory Failure.
Awake prone positioning research focuses primarily on improving oxygenation and reducing intubation and mortality rates. Secondary outcomes concerning patient safety have been poorly addressed. To summarize current evidence on the frequency of adverse events during awake prone positioning and the effects on patients' safety, comfort, and tolerance. This scoping review used the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews. MEDLINE/PubMed and CINAHL databases were the primary sources for the systematic search. The review included 19 original studies involving 949 patients who underwent awake prone positioning. No major complications such as death, severe respiratory compromise, or hemodynamic disease were reported. Ten studies reported the following secondary adverse events related to awake prone positioning: skin breakdown (1%-6% of patients), pain (12%-42%), discomfort (35%-43%), vomiting (2%-7%), intolerance (3%-47%), and vascular catheter dislodgment (5%). The duration of awake prone positioning sessions varied widely (0.3-19 hours). Seven studies reported that nurses helped patients during prone positioning maneuvers, including monitoring and surveillance, and 3 studies reported patients placing themselves in the prone position. In 6 studies light or moderate sedation was employed in the procedures. Awake prone positioning was not related to cardiorespiratory consequences but was associated with pain, intolerance, discomfort, and patients' refusal. Patients should receive education regarding awake prone positioning to improve their acceptance. Health care professionals should optimize pain control, communication, patient comfort, patient adherence, and correct positioning.


Children exposed to intimate partner violence and the reported effects of psychosocial interventions.
Using a repeated measures design posttraumatic stress (PTS), psychological and behavioral problems significantly decreased following intervention in children exposed to intimate partner violence (IPV), with use of traditional group analyses. Analyses using the reliable change index (RCI), however, revealed that few children were improved or recovered, implying that interventions in common use should be evaluated for their significant impact on the individual level in addition to group level statistics. Positive changes in children's behavioral problems were related to the mother's improvement of their own mental health. Direct victimization by the perpetrator was not associated with treatment changes but with higher symptom levels at study entry. Amount of contact with the perpetrator was neither related to symptom load nor to changes following treatment.


The TryPIKinome of five human pathogenic trypanosomatids: Trypanosoma brucei, Trypanosoma cruzi, Leishmania major, Leishmania braziliensis and Leishmania infantum--new tools for designing specific inhibitors.
Phosphatidylinositol (PI) kinases are at the heart of one of the major pathways of intracellular signal transduction. Herein, we present the first report on a survey made by similarity searches against the five human pathogenic trypanosomatids Trypanosoma brucei, Trypanosoma cruzi, Leishmania major, Leishmania braziliensis and Leishmania infantum genomes available to date for phosphatidylinositol- and related-kinases (TryPIKs). In addition to generating a panel called "The TryPIKinome", we propose a model of signaling pathways for these TryPIKs. The involvement of TryPIKs in fundamental pathways, such as intracellular signal transduction and host invasion processes, makes the study of TryPIKs an important area for further inquiry. New subtype-specific inhibitors are expected to work on individual members of the PIK family and, therefore, can presumably neutralize trypanosomatid invasion processes.


Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis.
Currently ketogenic diets (KDs) are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice. We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD). For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95% HPDI = [0.26, 0.87]), indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation) which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04]). There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.


Core outcome domains for clinical trials in non-specific low back pain.
Inconsistent reporting of outcomes in clinical trials of patients with non-specific low back pain (NSLBP) hinders comparison of findings and the reliability of systematic reviews. A core outcome set (COS) can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials. In 1998, Deyo et al. recommended a standardized set of outcomes for LBP clinical research. The aim of this study was to update these recommendations by determining which outcome domains should be included in a COS for clinical trials in NSLBP. An International Steering Committee established the methodology to develop this COS. The OMERACT Filter 2.0 framework was used to draw a list of potential core domains that were presented in a Delphi study. Researchers, care providers and patients were invited to participate in three Delphi rounds and were asked to judge which domains were core. A priori criteria for consensus were established before each round and were analysed together with arguments provided by panellists on importance, overlap, aggregation and/or addition of potential core domains. The Steering Committee discussed the final results and made final decisions. A set of 280 experts was invited to participate in the Delphi; response rates in the three rounds were 52, 50 and 45%. Of 41 potential core domains presented in the first round, 13 had sufficient support to be presented for rating in the third round. Overall consensus was reached for the inclusion of three domains in this COS: 'physical functioning', 'pain intensity' and 'health-related quality of life'. Consensus on 'physical functioning' and 'pain intensity' was consistent across all stakeholders, 'health-related quality of life' was not supported by the patients, and all the other domains were not supported by two or more groups of stakeholders. Weighting all possible argumentations, the Steering Committee decided to include in the COS the three domains that reached overall consensus and the domain 'number of deaths'. The following outcome domains were included in this updated COS: 'physical functioning', 'pain intensity', 'health-related quality of life' and 'number of deaths'. The next step for the development of this COS will be to determine which measurement instruments best measure these domains.


Whole-body PET/CT scanning: estimation of radiation dose and cancer risk.
To estimate the radiation dose from whole-body fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomographic (PET)/computed tomographic (CT) studies and to evaluate the induced cancer risk to U.S. and Hong Kong populations. Fluorine 18-FDG PET/CT studies obtained by using a 64-detector CT unit and one of three CT protocols were evaluated. CT protocol A consisted of 120 kV; rotation time, 0.5 second; pitch, 0.984; 100-300 mA; and noise level, 20. CT protocol B was the same as A, except for a fixed tube current of 250 mA. CT protocol C consisted of 140 kV; rotation time, 0.5 second; pitch, 0.984; 150-350 mA; and noise level, 3.5. CT doses were measured in a humanoid phantom equipped with thermoluminescent dosimeters. Doses from (18)F-FDG PET scanning were estimated by multiplying the (18)F-FDG radioactivity (370 MBq) with dose coefficients. Effective doses were calculated according to International Commission on Radiological Protection publication 103. Lifetime attributable risk (LAR) of cancer incidence was estimated according to the National Academies' Biological Effects of Ionizing Radiation VII Report. Effective doses with protocols A, B, and C, respectively, were 13.45, 24.79, and 31.91 mSv for female patients and 13.65, 24.80, and 32.18 mSv for male patients. The LAR of cancer incidence associated with the dose was higher in the Hong Kong population than in the U.S. population. For 20-year-old U.S. women, LARs of cancer incidence were between 0.231% and 0.514%, and for 20-year-old U.S. men, LARs of cancer incidence were between 0.163% and 0.323%; LARs were 5.5%-20.9% higher for the Hong Kong population. The induced cancer risks decreased when age at exposure increased. Whole-body PET/CT scanning is accompanied by substantial radiation dose and cancer risk. Thus, examinations should be clinically justified, and measures should be taken to reduce the dose.


Relapse risk after discontinuation of risperidone in Alzheimer's disease.
Among patients with Alzheimer's disease who have had a response to antipsychotic medication for psychosis or agitation-aggression, the risk of a recurrence of symptoms after discontinuation of the medication has not been established. Patients with Alzheimer's disease and psychosis or agitation-aggression received open-label treatment with risperidone for 16 weeks. Those who had a response to risperidone therapy were then randomly assigned, in a double-blind fashion, to one of three regimens: continued risperidone therapy for 32 weeks (group 1), risperidone therapy for 16 weeks followed by placebo for 16 weeks (group 2), or placebo for 32 weeks (group 3). The primary outcome was the time to relapse of psychosis or agitation. A total of 180 patients received open-label risperidone (mean dose, 0.97 mg daily). The severity of psychosis and agitation were reduced, although there was a mild increase in extrapyramidal signs; 112 patients met the criteria for response to treatment, of whom 110 underwent randomization. In the first 16 weeks after randomization, the rate of relapse was higher in the group that received placebo than in the groups that received risperidone (60% [24 of 40 patients in group 3] vs. 33% [23 of 70 in groups 1 and 2]; P=0.004; hazard ratio with placebo, 1.94; 95% confidence interval [CI], 1.09 to 3.45; P=0.02). During the next 16 weeks, the rate of relapse was higher in the group that was switched from risperidone to placebo than in the group that continued to receive risperidone (48% [13 of 27 patients in group 2] vs. 15% [2 of 13 in group 1]; P=0.02; hazard ratio, 4.88; 95% CI, 1.08 to 21.98; P=0.02). The rates of adverse events and death after randomization did not differ significantly among the groups, although comparisons were based on small numbers of patients, especially during the final 16 weeks. In patients with Alzheimer's disease who had psychosis or agitation that had responded to risperidone therapy for 4 to 8 months, discontinuation of risperidone was associated with an increased risk of relapse. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00417482.).


Acute treadmill exercise discriminately improves the skeletal muscle insulin-stimulated growth signaling responses in mice lacking REDD1.
A loss of the regulated in development and DNA damage 1 (REDD1) hyperactivates mechanistic Target of Rapamycin Complex 1 (mTORC1) reducing insulin-stimulated insulin signaling, which could provide insight into mechanisms of insulin resistance. Although aerobic exercise acutely inhibits mTORC1 signaling, improvements in insulin-stimulated signaling are exhibited. The goal of this study was to determine if a single bout of treadmill exercise was sufficient to improve insulin signaling in mice lacking REDD1. REDD1 wildtype (WT) and REDD1 knockout (KO) mice were acutely exercised on a treadmill (30 min, 20 m/min, 5% grade). A within animal noninsulin-to-insulin-stimulated percent change in skeletal muscle insulin-stimulated kinases (IRS-1, ERK1/2, Akt), growth signaling activation (4E-BP1, S6K1), and markers of growth repression (REDD1, AMPK, FOXO1/3A) was examined, following no exercise control or an acute bout of exercise. Unlike REDD1 KO mice, REDD1 WT mice exhibited an increase (P < 0.05) in REDD1 following treadmill exercise. However, both REDD1 WT and KO mice exhibited an increase (P < 0.05) AMPK phosphorylation, and a subsequent reduction (P < 0.05) in mTORC1 signaling after the exercise bout versus nonexercising WT or KO mice. Exercise increased (P < 0.05) the noninsulin-to-insulin-stimulated percent change phosphorylation of mTORC1, ERK1/2, IRS-1, and Akt on S473 in REDD1 KO mice when compared to nonexercised KO mice. However, there was no change in the noninsulin-to-insulin-stimulated percent change activation of Akt on T308 and FOXO1/3A in the KO when compared to WT or KO mouse muscle after exercise. Our data show that a bout of treadmill exercise discriminately improves insulin-stimulated signaling in the absence of REDD1.


Carbapenem-Resistant Enterobacteriaceae Infections: Taiwan Aspects.
Carbapenem-resistant Enterobacteriaceae (CRE), a major resistance concern emerging during the last decade because of significantly compromising the efficacy of carbapenem agents, has currently become an important focus of infection control. Many investigations have shown a high association of CRE infections with high case-fatality rates. In Taiwan, a few surveys observed that a significant proportion (29-47%) of the CR-Klebsiella pneumoniae isolates harbored a plasmidic allele encoding K. pneumoniae carbapenemases (KPC, especially KPC-2). A significant increase in the number of oxacillinase (OXA)-48-like carbapenemases among CR-K. pneumoniae isolates was observed between 2012 and 2015. By striking contrast, isolates of CR-Escherichia coli and CR-Enterobacter species in Taiwan had a much lower percentage of carbapenemase production than CR-K. pneumoniae isolates. This differs from isolates found in China as well as in the India subcontinent. Apart from the hospital setting, CRE was also cultured from the inpatients from communities or long-term care facilities (LTCF). Therefore, implementation of regular CRE screening of LTCF residents, strict disinfectant use in nursing homes and hospital settings, and appropriate control of antibiotic prescriptions is suggested to alleviate the spread of clinical CRE isolates in Taiwan. Although there are some promising new antibiotics against CRE, such as ceftazidime-avibactam, meropenem-vaborbactam, aztreonam-avibactam and cefiderocol, these agents are not available in Taiwan currently. Therefore, in order to effectively decrease case-fatality rates among patients with the infections owing to carbapenemase-producing CRE isolates, combination antibiotic schemes, including colistin (or amikacin) and/or tigecycline in combination with an anti-pseudomonal carbapenem agent, remain the mainstay for treating clinical CRE infections.


Bipolar affective psychosis with onset before age 16 years: report of 10 cases.
Ten patients, 5 male and 5 female, with bipolar psychosis beginning before the age of 16 years, mean 14.1 years, are described. Difficulties in diagnosis in this age group are discussed and background factors of possible aetiological importance analysed. Lithium therapy was effective in 6 out of 7 patients.


Normality: Part descriptive, part prescriptive.
People's beliefs about normality play an important role in many aspects of cognition and life (e.g., causal cognition, linguistic semantics, cooperative behavior). But how do people determine what sorts of things are normal in the first place? Past research has studied both people's representations of statistical norms (e.g., the average) and their representations of prescriptive norms (e.g., the ideal). Four studies suggest that people's notion of normality incorporates both of these types of norms. In particular, people's representations of what is normal were found to be influenced both by what they believed to be descriptively average and by what they believed to be prescriptively ideal. This is shown across three domains: people's use of the word "normal" (Study 1), their use of gradable adjectives (Study 2), and their judgments of concept prototypicality (Study 3). A final study investigated the learning of normality for a novel category, showing that people actively combine statistical and prescriptive information they have learned into an undifferentiated notion of what is normal (Study 4). Taken together, these findings may help to explain how moral norms impact the acquisition of normality and, conversely, how normality impacts the acquisition of moral norms.


[Students' physical activity: an analysis according to Pender's health promotion model].
The objective of this study was to describe the everyday physical activity habits of students and analyze the practice of physical activity and its determinants, based on the first component of Pender's health promotion model. This cross-sectional study was performed from 2004 to 2005 with 79 students in a public school in Fortaleza, Ceará, Brazil. Data collection was performed by interviews and physical examinations. The data were analyzed according to the referred theoretical model. Most students (n=60) were physically active. Proportionally, adolescents were the most active (80.4%). Those with a sedentary lifestyle had higher rates for overweight and obesity (21.1%). Many students practiced outdoor physical activities, which did not require any physical structure and good financial conditions. The results show that it is possible to associate the first component of Pender's health promotion model with the everyday lives of students in terms of the physical activity practice.


Comorbidity in posttraumatic stress disorder: a structural equation modelling approach.
Posttraumatic stress disorder (PTSD) is associated with high rates of psychiatric comorbidity. Existing theories consider comorbidity as a consequence of PTSD (model 1), PTSD and comorbidity as a consequence of shared factors of vulnerability (model 2), and comorbidity as a consequence of trauma-type specific mechanisms (model 3). To compare the explanatory value of these models, we assessed PTSD (model 1), sense of coherence (model 2) and satisfaction with health (model 3) and symptoms of anxiety and depression as indicators of comorbidity 5 days (t1) and 6 months (t2) postaccident in 225 injured accident survivors. Structural equation models representing models 1 to 3 were tested separately and combined. Combined, models 1 and 3 explained 82% of the variance of comorbid symptoms at t2. Posttraumatic stress disorder and satisfaction with health (t2) exerted strong influences on comorbid symptoms. Comorbidity besides PTSD is best described by an integration of competing explanatory models.


Global geometric affinity for revealing high fidelity protein interaction network.
Protein-protein interaction (PPI) network analysis presents an essential role in understanding the functional relationship among proteins in a living biological system. Despite the success of current approaches for understanding the PPI network, the large fraction of missing and spurious PPIs and a low coverage of complete PPI network are the sources of major concern. In this paper, based on the diffusion process, we propose a new concept of global geometric affinity and an accompanying computational scheme to filter the uncertain PPIs, namely, reduce the spurious PPIs and recover the missing PPIs in the network. The main concept defines a diffusion process in which all proteins simultaneously participate to define a similarity metric (global geometric affinity (GGA)) to robustly reflect the internal connectivity among proteins. The robustness of the GGA is attributed to propagating the local connectivity to a global representation of similarity among proteins in a diffusion process. The propagation process is extremely fast as only simple matrix products are required in this computation process and thus our method is geared toward applications in high-throughput PPI networks. Furthermore, we proposed two new approaches that determine the optimal geometric scale of the PPI network and the optimal threshold for assigning the PPI from the GGA matrix. Our approach is tested with three protein-protein interaction networks and performs well with significant random noises of deletions and insertions in true PPIs. Our approach has the potential to benefit biological experiments, to better characterize network data sets, and to drive new discoveries.


Accuracy of whole blood glucose measurement when venous catheter blood samples are used on glucose meters.
Previous studies have found positive bias and frequent outliers when central venous catheter (CVC) whole blood is used to dose glucose meters. We designed a study to determine whether positive bias and outliers with CVC whole blood glucose samples are due to exogenous glucose contamination of CVC samples, inherent bias and imprecision of glucose meters, or properties of CVC whole blood that interfere with the function of some glucose meters. We studied the relationship between venous whole blood and venous plasma glucose drawn by venipuncture to CVC whole blood and CVC plasma glucose in 50 hospitalized patients. In 27 patients whole blood glucose was measured on both the Accu-Chek Inform (Roche Diagnostics, Indianapolis, IN) and StatStrip (Nova Biomedical, Waltham, MA). By comparing CVC plasma to venous plasma glucose, we determined that contamination of CVC samples with exogenous glucose was uncommon. On the Inform meter outliers were approximately twice as common with CVC whole blood compared to venous whole blood. In 27 patients who had CVC whole blood analyzed by both Inform and StatStrip, outliers occurred approximately twice as often on the Inform compared to the StatStrip. Accounting for CVC samples contaminated with exogenous glucose, outliers on the StatStrip did not occur significantly more often using CVC whole blood compared to venous whole blood. Properties unique to CVC whole blood differentially affect glucose meter bias and imprecision. Device selection is critical in practices that wish to use CVC whole blood to monitor glucose concentration in hospitalized patients.


Chronic hepatitis C viral infection subverts vaccine-induced T-cell immunity in humans.
Adenoviral vectors encoding hepatitis C virus (HCV) nonstructural (NS) proteins induce multispecific, high-magnitude, durable CD4(+) and CD8(+) T-cell responses in healthy volunteers. We assessed the capacity of these vaccines to induce functional HCV-specific immune responses and determine T-cell cross-reactivity to endogenous virus in patients with chronic HCV infection. HCV genotype 1-infected patients were vaccinated using heterologous adenoviral vectors (ChAd3-NSmut and Ad6-NSmut) encoding HCV NS proteins in a dose escalation, prime-boost regimen, with and without concomitant pegylated interferon-α/ribavirin therapy. Analysis of immune responses ex vivo used human leukocyte antigen class I pentamers, intracellular cytokine staining, and fine mapping in interferon-γ enzyme-linked immunospot assays. Cross-reactivity of T cells with population and endogenous viral variants was determined following viral sequence analysis. Compared to healthy volunteers, the magnitude of HCV-specific T-cell responses following vaccination was markedly reduced. CD8(+) HCV-specific T-cell responses were detected in 15/24 patients at the highest dose, whereas CD4(+) T-cell responses were rarely detectable. Analysis of the host circulating viral sequence showed that T-cell responses were rarely elicited when there was sequence homology between vaccine immunogen and endogenous virus. In contrast, T cells were induced in the context of genetic mismatch between vaccine immunogen and endogenous virus; however, these commonly failed to recognize circulating epitope variants and had a distinct partially functional phenotype. Vaccination was well tolerated but had no significant effect on HCV viral load. Vaccination with potent HCV adenoviral vectored vaccines fails to restore T-cell immunity except where there is genetic mismatch between vaccine immunogen and endogenous virus; this highlights the major challenge of overcoming T-cell exhaustion in the context of persistent antigen exposure with implications for cancer and other persistent infections.


Pump power dependence of femtosecond two-color optical Kerr shutter measurements.
We investigated the pump power dependence of femtosecond two-color optical Kerr shutter (OKS) signals, which showed a damped sinusoidal variation with increasing pump power. The sinusoidal dependence was attributed to the polarization rotation caused by light-induced birefringence effect. The numerical analysis indicated that, the damping of OKS signal intensity could be attributed to the temporal profile change of probe pulse passing through the OKS setup, due to the non-uniform transient refractive index change induced by pump pulse. Because of the large phase shift of probe pulse, the time-resolved OKS signals showed modulated temporal intensity when pump power was increased.


Decreased expression of the endothelial cell-derived factor EGFL7 in systemic sclerosis: potential contribution to impaired angiogenesis and vasculogenesis.
Microvascular damage and defective angiogenesis and vasculogenesis have a major role in the pathogenesis of systemic sclerosis (SSc). Epidermal growth factor-like domain 7 (EGFL7) is a proangiogenic molecule which is predominantly expressed and secreted by endothelial cells and their progenitors and controls vascular development and integrity. In this study, we investigated the possible involvement of EGFL7 in SSc. Serum EGFL7 levels from 60 patients with SSc and 35 age- and sex-matched healthy controls were examined by colorimetric sandwich enzyme-linked immunosorbent assay. The expression of EGFL7 in forearm skin biopsies (n = 16 SSc, n = 10 controls), cultured dermal microvascular endothelial cells (MVECs) (n = 3 SSc, n = 3 controls) and late-outgrowth peripheral blood endothelial progenitor cell (EPC)-derived endothelial cells (n = 15 SSc, n = 8 controls) was investigated by immunofluorescence and Western blotting. Serum EGFL7 levels were detectable in 68.6% of healthy controls and 45% of SSc cases (P < 0.05). Circulating levels of EGFL7 were significantly decreased in SSc patients compared with healthy controls (P = 0.01). Serum levels of EGFL7 were significantly lower in both limited cutaneous SSc and diffuse cutaneous SSc patients than in controls (P = 0.02 and P = 0.04, respectively). In SSc, decreased serum EGFL7 levels were significantly correlated with the severity of nailfold capillary abnormalities. Patients with the most severe capillary changes and digital ulcers had serum EGFL7 levels significantly lower than healthy controls, while the EGFL7 levels did not differ significantly between controls and SSc patients with less capillary damage and lack of digital ulcers. Endothelial EGFL7 expression was strongly downregulated or even almost completely undetectable in SSc-affected dermis compared with controls (P < 0.001). In cultured SSc dermal MVECs and late-outgrowth peripheral blood EPC-derived endothelial cells, EGFL7 was significantly downregulated compared with cells obtained from healthy subjects (P < 0.01 and P < 0.001, respectively). Our findings suggest that the loss of EGFL7 expression in endothelial cells and their progenitors might play a role in the development and progression of peripheral microvascular damage and the defective vascular repair process characteristic of SSc.


Differential expression of mitochondrial genes between queens and workers during caste determination in the honeybee Apis mellifera.
The nourishment received by female honeybee larvae determines their differentiation into queens or workers. In this study, we report the first molecular analysis of differences that occur between queens and workers during the caste-determination process. RNA-differential display experiments identified a clone that encodes for a gene that is homologous to the nuclear-encoded mitochondrial translation initiation factor (AmIF-2mt). Semi-quantitative analysis by reverse transcriptase/polymerase chain reaction (RT-PCR) throughout honeybee development detected a higher level of expression of this gene in queen larvae than in worker larvae. Analysis of two other genes encoding mitochondrial proteins, cytochrome oxidase subunit 1 (COX-1; mitochondrial-encoded) and cytochrome c (cyt c; nuclear-encoded) also showed differential expression of these two genes between queens and workers. In particular, the cyt c transcript is more abundant in queen larvae and throughout the metamorphosis of the queen. These results indicate that the higher respiratory rate previously documented in queen larvae is accomplished through a higher level of expression of both nuclear- and mitochondrial-encoded genes for mitochondrial proteins.


Asian American, Native Hawaiian and Pacific Islander tobacco use patterns.
To provide a national depiction of Asian American (AA) and Native Hawaiian/Pacific Islander (NHPI) tobacco use and highlight considerations for targeted interventions. We analyzed data from the 2009-2010 National Adult Tobacco Survey for subgroup differences in prevalence and consumption of various tobacco products. Use varies considerably by ethnic subgroups for cigarette smoking (including menthol) and other forms of tobacco. Despite being lighter, less frequent, and seemingly less dependent smokers, AANHPIs had similar quit ratios as non-AANHPIs. AA and NHPI disparities in tobacco use may be due to underutilization of cessation resources, including those for non-cigarette tobacco products, and lack of availability of culturally-appropriate resources. Community-based and regulatory approaches should be employed to reduce use of all tobacco products, especially among high prevalence subgroups.


Subfornical organ. Does it protect against angiotensin II-induced hypertension in the rat?
The purpose of this study was to examine the contribution of the subfornical organ to the chronic hypertension produced by intravenous angiotensin II infusion in rats. Male rats were instrumented with permanent arterial and venous catheters and housed in metabolism cages for daily measurement of arterial pressure, heart rate, water intake, water balance, and urinary electrolyte excretion. Angiotensin II was infused intravenously at a rate of 10 ng/minute for 5 consecutive days, preceded by 2 control days, and followed by 2 recovery days. Normal rats with an intact subfornical organ (n = 7), and rats with an electrolytic lesion placed such that greater than 80% of the subfornical organ was destroyed (n = 9), were studied using this infusion protocol. An additional group of eight rats did not receive angiotensin II, and, thus, served as a time control. Both groups of rats receiving angiotensin II exhibited significant elevations in arterial pressure during the 5-day hormone infusion period, but pressure in rats with subfornical organ lesions (delta 23-29 mm Hg) was increased significantly more than that of intact rats (delta 14-20 mm Hg). Water intake was significantly increased on the 3rd, 4th, and 5th days of angiotensin II infusion only in rats with lesions in the subfornical organ. In contrast to previous studies showing that an intact subfornical organ is required for normal pressor and drinking responses to acute elevations in circulating angiotensin II in the rat, the current experiments indicate that the presence of the subfornical organ actually inhibits these same responses during more chronic increases in plasma angiotensin II levels.


Mesenchymal stem cells for the treatment of neurodegenerative disease.
Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for cell therapy, and are currently being tested in US FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. They have been extensively tested and proven effective in preclinical studies for these and many other disorders. There is currently a great deal of interest in the use of MSCs to treat neurodegenerative diseases, in particular for those that are fatal and difficult to treat, such as Huntington's disease and amyotrophic lateral sclerosis. Proposed regenerative approaches to neurological diseases using MSCs include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs promote endogenous neuronal growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize on the innate trophic support from MSCs or on augmented growth factor support, such as delivering brain-derived neurotrophic factor or glial-derived neurotrophic factor into the brain to support injured neurons, using genetically engineered MSCs as the delivery vehicles. Clinical trials for MSC injection into the CNS to treat traumatic brain injury and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of neurodegenerative disorders are discussed.


Genetic signature of adaptive peak shift in threespine stickleback.
Transition of an evolving population to a new adaptive optimum is predicted to leave a signature in the distribution of effect sizes of fixed mutations. If they affect many traits (are pleiotropic), large effect mutations should contribute more when a population evolves to a farther adaptive peak than to a nearer peak. We tested this prediction in wild threespine stickleback fish (Gasterosteus aculeatus) by comparing the estimated frequency of large effect genetic changes underlying evolution as the same ancestor adapted to two lake types since the end of the ice age. A higher frequency of large effect genetic changes (quantitative trait loci) contributed to adaptive evolution in populations that adapted to lakes representing a more distant optimum than to lakes in which the optimum phenotype was nearer to the ancestral state. Our results also indicate that pleiotropy, not just optimum overshoot, contributes to this difference. These results suggest that a series of adaptive improvements to a new environment leaves a detectable mark in the genome of wild populations. Although not all assumptions of the theory are likely met in natural systems, the prediction may be robust enough to the complexities of natural environments to be useful when forecasting adaptive responses to large environmental changes.


Regenerative endodontic procedure combined with non-surgical root canal treatment in an immature permanent maxillary molar: A 7-year follow-up case report.
The aim of this report is to present the results of a personalised endodontic treatment for an immature molar, using regenerative endodontic procedure (REP) combined with non-surgical root canal treatment (NSRCT), with 7 years of follow-up. The tooth#3 presented combined endodontic pathologies in each root, with different pulpal and periapical status. A REP in the palatal (P) canal and a NSCRT in the mesio-buccal (MB) and disto-buccal (DB) canals were performed. Absence of clinical signs/symptoms and continuous palatal root development with apical closure were observed over 4-years. After 5-years an apical lesion in the MB root was observed. Both MB canals were selectively retreated by completely filling them with TotalFill BC RRM Fast Set putty. After 7-years, the tooth remained functional and the apical lesion was resolving. The palatal root was completely mature. This case report reveals the potential for use of combined treatment approaches for immature multirooted teeth.


Role for ADP ribosylation factor 1 in the regulation of hepatitis C virus replication.
We hypothesized that ADP-ribosylation factor 1 (Arf1) plays an important role in the biogenesis and maintenance of infectious hepatitis C virus (HCV). Huh7.5 cells, in which HCV replicates and produces infectious viral particles, were exposed to brefeldin A or golgicide A, pharmacological inhibitors of Arf1 activation. Treatment with these agents caused a reduction in viral RNA levels, the accumulation of infectious particles within the cells, and a reduction in the levels of these particles in the extracellular medium. Fluorescence analyses showed that the viral nonstructural (NS) proteins NS5A and NS3, but not the viral structural protein core, shifted their localization from speckle-like structures in untreated cells to the rims of lipid droplets (LDs) in treated cells. Using pulldown assays, we showed that ectopic overexpression of NS5A in Huh7 cells reduces the levels of GTP-Arf1. Downregulation of Arf1 expression by small interfering RNA (siRNA) decreased both the levels of HCV RNA and the production of infectious viral particles and altered the localization of NS5A to the peripheries of LDs. Together, our data provide novel insights into the role of Arf1 in the regulation of viral RNA replication and the production of infectious HCV.


Quantum quench of Kondo correlations in optical absorption.
The interaction between a single confined spin and the spins of an electron reservoir leads to one of the most remarkable phenomena of many-body physics--the Kondo effect. Electronic transport measurements on single artificial atoms, or quantum dots, have made it possible to study the effect in great detail. Here we report optical measurements on a single semiconductor quantum dot tunnel-coupled to a degenerate electron gas which show that absorption of a single photon leads to an abrupt change in the system Hamiltonian and a quantum quench of Kondo correlations. By inferring the characteristic power-law exponents from the experimental absorption line shapes, we find a unique signature of the quench in the form of an Anderson orthogonality catastrophe, induced by a vanishing overlap between the initial and final many-body wavefunctions. We show that the power-law exponent that determines the degree of orthogonality can be tuned using an external magnetic field, which unequivocally demonstrates that the observed absorption line shape originates from Kondo correlations. Our experiments demonstrate that optical measurements on single artificial atoms offer new perspectives on many-body phenomena previously studied using transport spectroscopy only.


Antecedents of Suicide among Youth Aged 11-15: A Multistate Mixed Methods Analysis.
Suicide is the second leading cause of death for youth aged 11 to 15, taking over 5,500 lives from 2003 to 2014. Suicide among this age group is linked to risk factors such as mental health problems, family history of suicidal behavior, biological factors, family problems, and peer victimization and bullying. However, few studies have examined the frequency with which such problems occur among youth suicide decedents or the context in which decedents experience these risk factors and the complex interplay of risk that results in a decedent's decision to take his/her own life. Data from a random sample of 482 youth (ages 11-15) suicide cases captured in the National Violent Death Reporting System from 2003 to 2014 were analyzed. The sample had fewer girls than boys (31 vs. 69 %) and comprised primarily White youth (79 %), but also African Americans (13 %), Asians (4 %), and youth of other races (4 %). Narrative data from coroner/medical examiner and law enforcement investigative reports were coded and analyzed to identify common behavioral patterns that preceded suicide. Emergent themes were quantified and examined using content and constant comparative analysis. Themes regarding antecedents across multiple levels of the social ecology emerged. Relationship problems, particularly with parents, were the most common suicide antecedent. Also, a pattern demonstrating a consistent progression toward suicidal behavior emerged from the data. Narratives indicated that youth were commonly exposed to one or more problems, often resulting in feelings of loneliness and burdensomeness, which progressed toward thoughts and sometimes plans for or attempts at suicide. Continued exposure to negative experiences and thoughts/plans about suicide, and/or self-injurious acts resulted in an acquired capacity to self-harm, eventually leading to suicide. These findings provide support for theories of suicidal behavior and highlight the importance of multi-level, comprehensive interventions that address individual cognitions and build social connectedness and support, as well as prevention strategies that increase awareness of the warning signs and symptoms of suicide, particularly among family members of at-risk youth.


Chronic respiratory mycoplasmosis in C3H/HeN and C57BL/6N mice: lesion severity and antibody response.
Mycoplasma pneumoniae is a leading, worldwide cause of death and disability due to pneumonia. Mycoplasma pulmonis infection in mice is an invaluable model for the study of host defenses against respiratory mycoplasmas in vivo. C3H/HeN mice are much more susceptible to acute inflammatory lung disease due to M. pulmonis than C57BL/6N mice, but little is known about the chronic disease in these mouse strains. We infected C3H/HeN and C57BL/6N mice with 10(4) CFU of M. pulmonis UAB CT and evaluated them at weekly intervals by quantitative mycoplasma culture of nasal passages, trachea, and lungs, assessment of lesion severity in nasal passages, trachea, and lungs, and determination of serum immunoglobulin classes and subclasses by enzyme-linked immunosorbent assay. We found that C3H/HeN mice had 2 to 5 logs more organisms in their lungs and far more severe lung disease than C57BL/6N mice through 63 days postinfection. Although both strains of mice developed the same classes of antibody, C3H/HeN mice had much greater anti-M. pulmonis immunoglobulin G (IgG) responses in the IgG1 and IgG2a subclasses than C57BL/6N mice. These results suggest that adaptive immunity does not effect resolution of chronic mycoplasma infection and disease in the lungs.


Age-related Morbidity and Mortality After Transjugular Intrahepatic Portosystemic Shunts.
To compare age-related morbidity and mortality after transjugular intrahepatic portosystemic shunts (TIPS). We performed a retrospective chart review of patients who underwent TIPS at the University of California Los Angeles Medical Center between 2008 to 2014. Elderly patients (65 y and older) were matched with nonelderly patients (controls, below 65 y) by model for end-stage liver disease (MELD) score (±3), indication for TIPS (refractory ascites vs. variceal bleeding), serum sodium level (±5), in a ratio of 1:1. Endpoints measures were hospital stay post-TIPS, rifaximin, or lactulose use, TIPS failure at 30 days, readmission at 90 days, MELD at 90 days, and mortality at 90 days. A total of 30 patient matches were included in this study: 30 control and 30 elderly patients. The median [interquartile (IQR)] MELD scores for controls and elderly were 11 (9, 13.8) for the controls and 11.5 (9, 14.8) for elderly patients (P=0.139). There were no significant differences in serum sodium and indication for TIPS. Thirty and 90-day follow-up laboratory test results were also similar between elderly and control patients. Event-free survival at 90 days was similar between controls and elderly patients [odds ratio (OR), 0.86; 95% confidence interval (CI), 0.3-2.5; P>0.05]. There was a trend toward greater hospitalization (OR, 1.76; 95% CI, 0.52-5.95; P=0.546) and mortality (OR, 3.3; 95% CI, 0.3-14.01; P=0.182). The results of this study suggest event-free survival is similar between nonelderly and elderly patients. Although statistically significant, there is a tendency toward greater mortality and hospitalization in the elderly.


The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis.
Rac1b, an alternative splice form of Rac1, has been previously shown to be upregulated in colon and breast cancer cells, suggesting an oncogenic role for Rac1b in these cancers. Our analysis of NSCLC tumor and matched normal tissue samples indicates Rac1b is upregulated in a significant fraction of lung tumors in correlation with mutational status of K-ras. To directly assess the oncogenic potential of Rac1b in vivo, we employed a mouse model of lung adenocarcinoma, in which the expression of Rac1b can be conditionally activated specifically in the lung. Although expression of Rac1b alone is insufficient to drive tumor initiation, the expression of Rac1b synergizes with an oncogenic allele of K-ras resulting in increased cellular proliferation and accelerated tumor growth. Finally, we show that in contrast to our previous findings demonstrating a requirement for Rac1 in K-ras-driven cell proliferation, Rac1b is not required in this context. Given the partially overlapping spectrum of downstream effectors regulated by Rac1 and Rac1b, our findings further delineate the signaling pathways downstream of Rac1 that are required for K-ras driven tumorigenesis.


Allopurinol and global left myocardial function in heart failure patients.
Increased xanthine oxidase (XO) activity may contribute to heart failure pathophysiology. This study evaluated whether a XO inhibitor, allopurinol produces clinical and functional benefits in patients with New York Heart Association functional class III to IV heart failure due to systolic dysfunction receiving optimal medical therapy as estimated by global left myocardial function. Fifty-nine patients with a diagnosis of chronic heart failure due to coronary heart disease or idiopathic dilated cardiomyopathy and 20 healthy controls who attended the outpatient clinic of cardiology were subjected to full echocardiographic study including left ventricular diastolic and systolic function, and the combined index of myocardial performance [Tei index: isovolumetric relaxation time (IRT) + isovolumetric contraction time (ICT)/ejection time (ET)]. Patients were randomized to allopurinol (300 mg/day) or placebo. Improvement at 36 weeks was assessed using a composite end point comprising global left cardiac function as well as heart failure morbidity and mortality. The percentage of patients characterized as improved, unchanged, or worsened did not differ between those receiving allopurinol or placebo. Allopurinol reduced serum uric acid (SUA) by 1.5 mg/dL (P = 0.001). In a subgroup analysis, patients with elevated SUA (more than 7mg/ dL) responded favorably to allopurinol whereas those with SUA less than 7mg/dL exhibited a trend toward no change. In addition, SUA reduction to allopurinol correlated with favorable clinical and functional response. Within the entire allopurinol patient cohort, those characterized as either improved or unchanged had significantly greater reductions in SUA compared with patients who did not change (P = 0.0007). In placebo patients, lower baseline SUA, but not change in SUA, correlated with improved clinical outcome. Allopurinol did not produce significant clinical and functional improvement in unselected patients with moderate-to-severe heart failure. However, it is suggested that it is useful in patients with elevated SUA in a manner according to degree of SUA reduction. SUA may serve as a valuable biomarker to target heart failure therapy.


MatrixDB: integration of new data with a focus on glycosaminoglycan interactions.
MatrixDB (http://matrixdb.univ-lyon1.fr/) is an interaction database focused on biomolecular interactions established by extracellular matrix (ECM) proteins and glycosaminoglycans (GAGs). It is an active member of the International Molecular Exchange (IMEx) consortium (https://www.imexconsortium.org/). It has adopted the HUPO Proteomics Standards Initiative standards for annotating and exchanging interaction data, either at the MIMIx (The Minimum Information about a Molecular Interaction eXperiment) or IMEx level. The following items related to GAGs have been added in the updated version of MatrixDB: (i) cross-references of GAG sequences to the GlyTouCan database, (ii) representation of GAG sequences in different formats (IUPAC and GlycoCT) and as SNFG (Symbol Nomenclature For Glycans) images and (iii) the GAG Builder online tool to build 3D models of GAG sequences from GlycoCT codes. The database schema has been improved to represent n-ary experiments. Gene expression data, imported from Expression Atlas (https://www.ebi.ac.uk/gxa/home), quantitative ECM proteomic datasets (http://matrisomeproject.mit.edu/ecm-atlas), and a new visualization tool of the 3D structures of biomolecules, based on the PDB Component Library and LiteMol, have also been added. A new advanced query interface now allows users to mine MatrixDB data using combinations of criteria, in order to build specific interaction networks related to diseases, biological processes, molecular functions or publications.


Anxiety, depression and post-traumatic stress disorder management after critical illness: a UK multi-centre prospective cohort study.
Survivors of critical illness have significant psychopathological comorbidity. The treatments offered by primary health care professionals to affected patients are unstudied. To report the psychological interventions after GPs received notification of patients who showed severe symptoms of anxiety, depression or Post-Traumatic Stress Disorder. Design: Multi-centre prospective cohort sub-study of the ICON study. NHS primary care in the United Kingdom. Adult patients, November 2006-October 2010 who had received at least 24 h of intensive care, where the general practitioner recorded notification that the patient had reported severe symptoms or caseness using the Hospital Anxiety and Depression Scale (HADS) or the Post-Traumatic Stress Disorder Check List-Civilian (PCL-C). We notified general practitioners (GPs) by post if a patient reported severe symptoms or caseness and sent a postal questionnaire to determine interventions after notification. Primary or secondary healthcare interventions instigated by general practitioners following notification of a patient's caseness. Of the 11,726 patients, sent questionnaire packs containing HADS and PCL-C, 4361 (37%) responded. A notification of severe symptoms was sent to their GP in 25% (1112) of cases. Of notified GPs, 65% (725) responded to our postal questionnaire. Of these 37% (266) had no record of receipt of the original notification. Of the 459 patients where GPs had record of notification (the study group for this analysis), 21% (98) had pre-existing psychopathology. Of those without a pre-existing diagnosis 45% (162) received further psychological assessment or treatment. GP screening or follow-up alone occurred in 18% (64) whilst 27% (98) were referred to mental health services or received drug therapy following notification. Postal questionnaire identifies a burden of psychopathology in survivors of critical illness that have otherwise gone undiagnosed following discharge from an intensive care unit (ICU). After being alerted to the presence of psychological symptoms, GPs instigate treatment in 27% and augmented surveillance in 18% of cases. ISRCTN69112866 (assigned 02/05/2006).


The purification, crystallization and preliminary structural characterization of glucose-1-phosphate thymidylyltransferase (RmlA), the first enzyme of the dTDP-L-rhamnose synthesis pathway from Pseudomonas aeruginosa.
Glucose-1-phosphate thymidylyltransferase (RmlA; E.C. 184.108.40.206) is the first of four enzymes involved in the biosynthesis of dTDP-L-rhamnose, the precursor of L-rhamnose, a key component of the cell wall of many pathogenic bacteria. RmlA catalyses the condensation of thymidine triphosphate (dTTP) and alpha-D-glucose-1-phosphate (G1P), yielding dTDP-D-glucose. RmlA from Pseudomonas aeruginosa has been overexpressed and purified. Crystals of the enzyme have been grown using the sitting-drop vapour-diffusion technique with PEG 6000 and lithium sulfate as precipitant. Several diffraction data sets of single frozen crystals were collected to a resolution of 1.66 A. Crystals belonged to space group P1, with unit-cell parameters a = 71.5, b = 73.1, c = 134.7 A, alpha = 89.9, beta = 80.9, gamma = 81.1 degrees. The asymmetric unit contains eight monomers in the form of two RmlA tetramers with a solvent content of 51%. Selenomethionine-labelled protein has been obtained and crystallized.


Nanoscale topography and spatial light modulator characterization using wide-field quantitative phase imaging.
We demonstrate an optical technique for large field of view quantitative phase imaging of reflective samples. It relies on a common-path interferometric design, which ensures high stability without the need for active stabilization. The technique provides single-shot, full-field and robust measurement of nanoscale topography of large samples. Further, the inherent stability allows reliable measurement of the temporally varying phase retardation of the liquid crystal cells, and thus enables real-time characterization of spatial light modulators. The technique's application potential is validated through experimental results.


Shanghai fever: a distinct Pseudomonas aeruginosa enteric disease.
Shanghai fever, a community-acquired enteric illness associated with sepsis caused by Pseudomonas aeruginosa, was first described in 1918. The understanding of Shanghai fever is incomplete. To delineate the clinical features and to examine the host and microbial factors associated with Shanghai fever. We prospectively enrolled 27 consecutive previously healthy children with community-acquired P aeruginosa enteritis and sepsis between July 2003 and June 2012. An immunological investigation, including measurement of serum immunoglobulin levels and lymphocyte subpopulations, was performed. The clonal relationship of bacterial isolates was determined by multilocus sequence typing (MLST) and the virulence of isolates was measured using cellular and animal models. The median age of the patients was 7 months; 24 (89%) were aged <1 year. The most common clinical manifestations were fever (100%), diarrhoea (96%) and shock (81%). Leucopenia, thrombocytopenia, high C-reactive protein levels, coagulopathy and hypoalbuminaemia were the key laboratory findings. Necrotising enteritis with or without bowel perforation, ecthyma gangrenosum and seizures were main complications. The death rate was 15%. No common primary immune deficiency was identified. MLST genotypes indicated that isolates from Shanghai fever were non-clonal, but they shared similar phenotypes which were invariably cytotoxic, invasive and adhesive in cellular experiments and caused prolonged gut colonisation and more death than respiratory and laboratory control strains in mice. Shanghai fever is a sporadic community-acquired disease of previously healthy infants that manifests as sepsis associated with P aeruginosa enteric disease. Both host and microbial factors play a role in pathogenesis.


Does host complement kill Borrelia burgdorferi within ticks?
The Lyme disease spirochete, Borrelia burgdorferi, inhabits the gut lumen of the tick vector. At this location the spirochete is exposed to host blood when a tick feeds. We report here on studies that were done with normal and complement-deficient (C3-knockout) mice to determine if the host complement system killed spirochetes within the vector. We found that spirochete numbers within feeding nymphs were not influenced by complement, most likely because host complement was inactivated within the vector. The Lyme disease outer surface protein A (OspA) vaccine is a transmission-blocking vaccine that targets spirochetes in the vector. In experiments with mice hyperimmunized with OspA, complement was not required to kill spirochetes within nymphs and to block transmission from nymphs to the vaccinated host. However, host complement did enhance the ability of OspA antibody to block larvae from acquiring spirochetes. Thus, the effects of OspA antibody on nymphal transmission and larval acquisition appear to be based on different mechanisms.