A Comparison of Sugar Intake between Individuals with High and Low Trait Anxiety: Results from the NutriNet-Santé Study.

(1) Background: Dietary carbohydrates are likely correlated with mental health in general, and with anxiety in particular. Our aim was to investigate the cross-sectional relationship between trait anxiety and carbohydrate (especially sugar) intake in a large sample derived from the general French population. (2) Methods: The analyses included 20231 non-diabetic adults enrolled in the NutriNet-Santé e-cohort, who had completed the trait anxiety subscale of the Spielberger State-Trait Anxiety Inventory (T-STAI, 2013-2016) and who were subsequently divided into high and low trait anxiety groups (T-STAI cut-off of 40 points). Sugar-rich food and macronutrient intake was calculated from ≥3 self-administered 24-h dietary records. The association between trait anxiety and carbohydrate intake was evaluated by ANCOVA according to age category (<45 and ≥45 years). (3) Results: In the full sample, 7942 (39,3%) individuals fell into the high trait anxiety category. They were more likely to be women (82,2% versus 69,2%; p < 0,0001) and younger (mean age 51,6 versus 55,1 years; p < 0,0001) compared to the low trait anxiety group. In fully-adjusted models, high-anxiety individuals aged under 45 years had significantly higher mean consumption of added simple sugars (43,9 versus 42,3 g/d; p < 0,0007), whereas those aged over 45 years with high trait anxiety had significantly lower mean consumption of fruit (214,0 versus 219,5 g/d; p < 0,02) compared to their low-anxiety counterparts. (4) Conclusion: This cross-sectional study revealed modest age-specific associations between anxiety status and sugar intake among adults. Prospective studies with representative samples are needed to explore potential bi-directionality of the observed associations.

Decision making about healthcare-related tests and diagnostic test strategies. Paper 4: International guidelines show variability in their approaches.

OBJECTIVES: The objective of the study was to describe and compare current practices in developing guidelines about the use of healthcare-related tests and diagnostic strategies (HCTDS). STUDY DESIGN AND SETTING: We sampled 37 public health and clinical practice guidelines about HCTDS from various sources without language restrictions. RESULTS: Detailed descriptions of the systems used to assess the quality of evidence and develop recommendations were challenging to find within guidelines. We observed much variability among and within organizations with respect to how they develop recommendations about HCTDS. Twenty-four percent of the guidelines did not consider health benefits and harms but based decisions solely on test accuracy. We did not identify guidelines that described the main potential care pathways involving tests for a healthcare problem. In addition, we did not identify guidelines that systematically assessed, described, and referenced the evidence that linked test accuracy and patient-important outcomes. CONCLUSION: There is considerable variability among the processes used and factors considered in developing recommendations about the use of tests. This variability may be the cause for the disagreement we observed in recommendations about testing for the same condition.

Decision making about healthcare-related tests and diagnostic test strategies. Paper 2: a review of methodological and practical challenges.

OBJECTIVES: In this first of a series of five articles, we provide an overview of how and why healthcare-related tests and diagnostic strategies are currently applied. We also describe how our findings can be integrated with existing frameworks for making decisions that guide the use of healthcare-related tests and diagnostic strategies. STUDY DESIGN AND SETTING: We searched MEDLINE, references of identified articles, chapters in relevant textbooks, and identified articles citing classic literature on this topic. RESULTS: We provide updated frameworks for the potential roles and applications of tests with suggested definitions and practical examples. We also discuss study designs that are commonly used to assess tests' performance and the effects of tests on people's health. These designs include diagnostic randomized controlled trials and retrospective validation. We describe the utility of these and other currently suggested designs, which questions they can answer and which ones they cannot. In addition, we summarize the challenges unique to decision-making resulting from the use of tests. CONCLUSION: This overview highlights current challenges in the application of tests in decision-making in healthcare, provides clarifications, and informs the proposed solutions.

Decision making about healthcare-related tests and diagnostic test strategies. Paper 3: a systematic review shows limitations in most tools designed to assess quality and develop recommendations.

OBJECTIVES: The objective of this study was to identify and describe critical appraisal tools designed for assessing the quality of evidence (QoE) and/or strength of recommendations (SoRs) related to health care-related tests and diagnostic strategies (HCTDSs). STUDY DESIGN AND SETTING: We conducted a systematic review to identify tools applied in guidelines, methodological articles, and systematic reviews to assess HCTDS. RESULTS: We screened 5,534 titles and abstracts, 1,004 full-text articles, and abstracted data from 330 references. We identified 29 tools and 14 modifications of existing tools for assessing QoE and SoR. Twenty-three out of 29 tools acknowledge the importance of assessing the QoE and SoR separately, but in 8, the SoR is based solely on QoE. When making decisions about the use of tests, patient values and preferences and impact on resource utilization were considered in 6 and 8 tools, respectively. There is also confusion about the terminology that describes the various factors that influence the QoE and SoR. CONCLUSION: Although at least one approach includes all relevant criteria for assessing QoE and determining SoR, more detailed guidance about how to operationalize these assessments and make related judgments will be beneficial. There is a need for a better description of the framework for using evidence to make decisions and develop recommendations about HCTDS.

Systematic reviews and meta-analyses of the accuracy of HPV tests, visual inspection with acetic acid, cytology, and colposcopy.

BACKGROUND: Cervical cancer screening is offered to women to identify and treat cervical intraepithelial neoplasia (CIN). OBJECTIVES: To support WHO guidelines, a systematic review was performed to compare test accuracy of the HPV test, cytology (cervical smear), and unaided visual inspection with acetic acid (VIA); and to determine test accuracy of HPV and colposcopy impression. SEARCH STRATEGY: Medline and Embase were searched up to September 2012, and experts were contacted for references. SELECTION CRITERIA: Studies of at least 100 nonpregnant women (aged ≥18years) not previously diagnosed with CIN were included. DATA COLLECTION AND ANALYSIS: Two investigators independently screened and collected data. Pooled sensitivity and specificity, and absolute differences were calculated, and the quality of evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: High to moderate quality evidence was found. The greatest difference in overtreatment occurred with VIA instead of the cervical smear (58 more per 1000 women). Differences in missed treatment ranged from 2-5 per 1000 women. For 1000 women screened positive and then sent to colposcopy, 464 would be falsely diagnosed with CIN grade 2-3 and treated. CONCLUSIONS: Although differences in sensitivity between tests could be interpreted as large, absolute differences in missed diagnoses were small. By contrast, small differences in specificity resulted in fairly large absolute differences in overtreatment.

Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) stage 2-3 is a premalignant lesion that can progress to cervical cancer in 10-20 years if untreated. OBJECTIVES: To conduct systematic reviews of randomized and nonrandomized studies for effects of cryotherapy, loop electrosurgical excision procedure (LEEP), and cold knife conization (CKC) as treatment for CIN 2-3. SEARCH STRATEGY: Medline, Embase, and other databases were searched to February 2012 for benefits, and to July 2012 for harms. Additionally, experts were contacted. Keywords for CIN, cervical cancer, and the treatments were used. SELECTION CRITERIA: Studies of nonpregnant women 18 years or older not previously treated for CIN were included. DATA COLLECTION AND ANALYSIS: Two investigators independently screened and collected data. Relative risks and proportions were calculated and evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: Recurrence rate was 5.3% 12 months after cryotherapy or LEEP, and 1.4% after CKC. There seemed to be little or no differences in frequency of complications after LEEP or cryotherapy, but they occurred more often after CKC. Evidence suggests premature delivery is most common with CKC, but it also occurs after LEEP and cryotherapy. CONCLUSIONS: Despite a comprehensive search, there is very low quality evidence and often no evidence for important outcomes, including reproductive outcomes and complications. Studies assessing these outcomes are needed.

Decision-Making about Healthcare Related Tests and Diagnostic Strategies: User Testing of GRADE Evidence Tables.

OBJECTIVE: To develop guidance on what information to include and how to present it in tables summarizing the evidence from systematic reviews of test accuracy following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. METHODS: To design and refine the evidence tables, we used an iterative process based on the analysis of data from four rounds of discussions, feedback and user testing. During the final round, we conducted one-on-one user testing with target end users. We presented a number of alternative formats of evidence tables to participants and obtained information about users' understanding and preferences. RESULTS: More than 150 users participated in initial discussions and provided their formal and informal feedback. 20 users completed one-on-one user testing interviews. Almost all participants preferred summarizing the results of systematic reviews of test accuracy in tabular format rather than plain text. Users generally preferred less complex tables but found presenting sensitivity and specificity estimates only as too simplistic. Users found the presentation of test accuracy for several values of prevalence initially confusing but modifying table layout and adding sample clinical scenarios for each prevalence reduced this confusion. Providing information about clinical consequences of testing result was viewed as not feasible for authors of systematic reviews. CONCLUSION: We present the current formats for tables presenting test accuracy following the GRADE approach. These tables can be developed using GRADEpro guidelines development tool (www.guidelinedevelopment.org or www.gradepro.org) and are being further developed into electronic interactive tables that will suit the needs of different end users. The formatting of these tables, and how they influence result interpretation and decision-making will be further evaluated in a randomized trial.

Emergency department use and hospitalizations among homeless adults with substance dependence and mental disorders.

BACKGROUND: Homelessness, substance use, and mental disorders each have been associated with higher rates of emergency department (ED) use and hospitalization. We sought to understand the correlation between ED use, hospital admission, and substance dependence among homeless individuals with concurrent mental illness who participated in a 'Housing First' (HF) intervention trial. METHODS: The Vancouver At Home study consisted of two randomized controlled trials addressing homeless individuals with mental disorders who have "high" or "moderate" levels of need. Substance dependence was determined at baseline prior to randomization, using the Mini International Neuropsychiatric Interview diagnostic tool, version 6.0. To assess health service use, we reviewed the number of ED visits and the number of hospital admissions based on administrative data for six urban hospitals. Negative binomial regression modeling was used to test the independent association between substance dependence and health service use (ED use and hospitalization), adjusting for HF intervention, age, gender, ethnicity, education, duration of lifetime homelessness, mental disorders, chronic health conditions, and other variables that were selected a priori to be potentially associated with use of ED services and hospital admission. RESULTS: Of the 497 homeless adults with mental disorders who were recruited, we included 381 participants in our analyses who had at least 1 year of follow-up and had a personal health number that could be linked to administrative health data. Of this group, 59% (n = 223) met criteria for substance dependence. We found no independent association between substance dependence and ED visits or hospital admissions [rate ratio (RR) = 0.85; 95% CI 0.62-1.17 and RR = 1.21; 95% CI 0.83-1.77, respectively]. The most responsible diagnoses (defined as the diagnosis that accounts for the length of stay) for hospital admissions were schizo-affective disorder, schizophrenia-related disorder, or bipolar affective disorder; collectively reported in 48% (n = 263) of admissions. Fifteen percent (n = 84) of hospital admissions listed substance dependence as the most responsible diagnosis. CONCLUSIONS: Substance dependence was not independently associated with ED use or hospital admission among homeless adults with mental disorders participating in an HF trial. Hospital admissions among this cohort were primarily associated with severe mental disorders. TRIAL REGISTRATION: ISRCTN57595077 and ISRCTN66721740.

The modular structure of the inner-membrane ring component PrgK facilitates assembly of the type III secretion system basal body.

The type III secretion system (T3SS) is a large macromolecular assembly found at the surface of many pathogenic Gram-negative bacteria. Its role is to inject toxic "effector" proteins into the cells of infected organisms. The molecular details of the assembly of this large, multimembrane-spanning complex remain poorly understood. Here, we report structural, biochemical, and functional analyses of PrgK, an inner-membrane component of the prototypical Salmonella typhimurium T3SS. We have obtained the atomic structures of the two ring building globular domains and show that the C-terminal transmembrane helix is not essential for assembly and secretion. We also demonstrate that structural rearrangement of the two PrgK globular domains, driven by an interconnecting linker region, may promote oligomerization into ring structures. Finally, we used electron microscopy-guided symmetry modeling to propose a structural model for the intimately associated PrgH-PrgK ring interaction within the assembled basal body.

O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers.

The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). Previously, increased O-GlcNAcylation of tau has been shown to block the accumulation of tau aggregates within a tauopathy mouse model. Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. O-GlcNAcylation, however, does not impact the "global-fold" of tau as measured by a Förster resonance energy transfer assay. Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. This work further underscores the potential of targeting the O-GlcNAc pathway for potential Alzheimer's disease therapeutics.

Antivirals for influenza: a summary of a systematic review and meta-analysis of observational studies.

Despite the use of antivirals to treat patients with severe influenza, questions remain with respect to effects and safety. Although a recent systematic review has provided some indication of benefit, the analysis is limited by the quality of the available evidence from randomized controlled trials. To supplement the existing information, the authors conducted a systematic review of observational studies of antiviral treatment for influenza. This report summarises the findings of that review. Similar to the randomised trials, the confidence in the estimates of the effects for decision-making is low to very low primarily due to the risk of selection and publication bias in the observational studies. From these observational studies, the summary estimates suggest that oseltamivir may reduce mortality, hospitalisation and duration of symptoms compared with no treatment. Inhaled zanamivir may also reduce symptom duration and hospitalisations, but patients may experience more complications compared with no treatment. Earlier treatment with antivirals is generally associated with better outcomes than later treatment. Further high-quality evidence is needed to inform treatment guidelines because of the overall low to very low quality of evidence.

Investigating the structural dynamics of α-1,4-galactosyltransferase C from Neisseria meningitidis by nuclear magnetic resonance spectroscopy.

Neisseria meningitidis α-1,4-galactosyltransferase C (LgtC) is responsible for the transfer of α-galactose from donor UDP-galactose to the lipooligosaccharide terminal acceptor lactose. Crystal structures of its substrate analogue complexes have provided key insights into the galactosyl transfer mechanism, including a hypothesized need for active site mobility. Accordingly, we have used nuclear magnetic resonance spectroscopy to probe the structural dynamics of LgtC in its apo form and with bound substrate analogues. More than the expected number of signals were observed in the methyl-TROSY spectra of apo LgtC, indicating that the protein adopts multiple conformational states. Magnetization transfer experiments showed that the predominant states, termed "a" and "b", are in equilibrium on a time scale of seconds. Their relative populations change with temperature and mutations, and only the "b" state is competent for substrate binding. For both states, relaxation dispersion studies also revealed substantial millisecond time scale motions of isoleucine side chains within and distal to the active site. Although altered, these motions were still detected in LgtC with a noncovalently bound donor analogue. A mutant, LgtC-Q189E, which forms an unexpected glycosyl-enzyme intermediate via a residue (Asp190) distal from its active site, was also investigated. Apo LgtC-Q189E did not show any enhanced motions that might account for the dramatic structural change required for the galactosylation of Asp190, yet formation of a trapped glycosyl-enzyme intermediate substantially reduced its millisecond time scale conformational mobility. Although further studies are required to link the detected motions of LgtC with its enzymatic mechanism, this work clearly demonstrates the complex structural dynamics of a model glycosyltransferase.

Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies.

BACKGROUND: Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza. PURPOSE: To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists. STUDY SELECTION: Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness. DATA EXTRACTION: Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: 74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine. LIMITATIONS: Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias. CONCLUSION: Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and McMaster University.

Chemical sensing using fiber cavity ring-down spectroscopy.

Waveguide-based cavity ring-down spectroscopy (CRD) can be used for quantitative measurements of chemical concentrations in small amounts of liquid, in gases or in films. The change in ring-down time can be correlated to analyte concentration when using fiber optic sensing elements that change their attenuation in dependence of either sample absorption or refractive index. Two types of fiber cavities, i.e., fiber loops and fiber strands containing reflective elements, are distinguished. Both types of cavities were coupled to a variety of chemical sensor elements, which are discussed and compared.