Developing and testing a measure of consultation-based reassurance for people with low back pain in primary care:a cross-sectional study

BACKGROUND: Reassurance from physicians is commonly recommended in guidelines for the management of low back pain (LBP), but the process of reassurance and its impact on patients is poorly researched. We aimed to develop a valid and reliable measure of the process of reassurance during LBP consultations. METHODS: Items representing the data-gathering stage of the consultation and affective and cognitive reassurance were generated from literature on physician-patient communication and piloted with expert researchers and physicians, a Patient and Public Involvement group, and LBP patients to form a questionnaire. Patients presenting for LBP at 43 General Practice surgeries were sent the questionnaire. The questionnaire was analysed with Rasch modelling, using two samples from the same population of recent LBP consultations: the first (n = 157, follow-up n = 84) for exploratory analysis and the second (n = 162, follow-up n = 74) for confirmatory testing. Responses to the questionnaire were compared with responses to satisfaction and enablement scales to assess the external validity of the items, and participants completed the questionnaire again one-week later to assess test-retest reliability. RESULTS: The questionnaire was separated into four subscales: data-gathering, relationship-building, generic reassurance, and cognitive reassurance, each containing three items. All subscales showed good validity within the Rasch models, and good reliability based on person- and item-separations and test-retest reliability. All four subscales were significantly positively correlated with satisfaction and enablement for both samples. The final version of the questionnaire is presented here. CONCLUSIONS: Overall, the measure has demonstrated a good level of validity and generally acceptable reliability. This is the first measure to focus specifically on reassurance for LBP in primary care settings, and will enable researchers to further understanding of what is reassuring within the context of low back pain consultations, and how outcomes are affected by different types of reassurance. Additionally, the measure may provide a useful training and audit tool for physicians. The new measure requires testing in prospective cohorts, and would benefit from further validation against ethnographic observation of consultations in real time

Neuropathic Pain Phenotype Does Not Involve the NLRP3 Inflammasome and Its End Product Interleukin-1β in the Mice Spared Nerve Injury Model.

The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is one of the main sources of interleukin-1β (IL-1β) and is involved in several inflammatory-related pathologies. To date, its relationship with pain has not been studied in depth. The aim of our study was to elucidate the role of NLRP3 inflammasome and IL-1β production on neuropathic pain. Results showed that basal pain sensitivity is unaltered in NLRP3-/- mice as well as responses to formalin test. Spared nerve injury (SNI) surgery induced the development of mechanical allodynia and thermal hyperalgesia in a similar way in both genotypes and did not modify mRNA levels of the NLRP3 inflammasome components in the spinal cord. Intrathecal lipopolysaccharide (LPS) injection increases apoptosis-associated speck like protein (ASC), caspase-1 and IL-1β expression in both wildtype and NLRP3-/- mice. Those data suggest that NLRP3 is not involved in neuropathic pain and also that other sources of IL-1β are implicated in neuroinflammatory responses induced by LPS

Ancestry of the Brazilian TP53 c.1010G>A (p.Arg337His, R337H) founder mutation : clues from haplotyping of short tandem repeats on Chromosome 17p

Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial his- tory. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Ibe- ric origin, distant in about 72–84 generations (2000 years assuming a 25 years intergenera- tional distance) and thus pre-dating European migration to Brazil. So far, the founder p. Arg337His haplotype has not been detected outside Brazil, with the exception of two resi- dents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil.This study was funded by grant # 478430/2012-4 from CNPq (RFA MCT/CNPq - No 14/2012; Universal), Brazil.We would like to thank UFRGS, UFPA, AC Camargo, HC Barretos and University of Minho for their support during this work

Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms

Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration

Measurement of triple gauge-boson couplings at 172 GeV

The triple gauge-boson couplings, Awp, Aw and Abp, have been measured using 34 semileptonically and 54 hadronically decaying WW candidate events. The events were selected in the data recorded during 1996 with the ALEPH detector at 172 GeV, corresponding to an integrated luminosity of 10.65 pb^-1. The triple gauge-boson couplings have been measured using optimal observables constructed from kinematic information of WW events. The results are in agreement with the Standard Model expectation

Determination of sin2 θeff w using jet charge measurements in hadronic Z decays

The electroweak mixing angle is determined with high precision from measurements of the mean difference between forward and backward hemisphere charges in hadronic decays of the Z. A data sample of 2.5 million hadronic Z decays recorded over the period 1990 to 1994 in the ALEPH detector at LEP is used. The mean charge separation between event hemispheres containing the original quark and antiquark is measured for bb̄ and cc̄ events in subsamples selected by their long lifetimes or using fast D*'s. The corresponding average charge separation for light quarks is measured in an inclusive sample from the anticorrelation between charges of opposite hemispheres and agrees with predictions of hadronisation models with a precision of 2%. It is shown that differences between light quark charge separations and the measured average can be determined using hadronisation models, with systematic uncertainties constrained by measurements of inclusive production of kaons, protons and A's. The separations are used to measure the electroweak mixing angle precisely as sin2 θeff w = 0.2322 ± 0.0008(exp. stat.) ±0.0007(exp. syst.) ± 0.0008(sep.). The first two errors are due to purely experimental sources whereas the third stems from uncertainties in the quark charge separations

Anaerobe-enriched gut microbiota predicts pro-inflammatory responses in pulmonary tuberculosis

BACKGROUND: The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood. METHODS: To identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study. Microbiota were also characterised in close contacts of cases (CCCs, n = 73) and close contacts of SCs (CCSCs, n = 82) without active TB. FINDINGS: Cases and SCs each had similar α- and β-diversities in oral washes and sputum, however, β-diversity differed in stool (PERMANOVA p = 0•035). Cases were enriched with anaerobes in oral washes, sputum (Paludibacter, Lautropia in both) and stool (Erysipelotrichaceae, Blautia, Anaerostipes) and their stools enriched in microbial genes annotated as amino acid and carbohydrate metabolic pathways. In pairwise comparisons with their CCCs, cases had Megasphaera-enriched oral and sputum microbiota and Bifidobacterium-, Roseburia-, and Dorea-depleted stools. Compared to their CCSCs, SCs had reduced α-diversities and many differential taxa per specimen type. Cases differed transcriptionally from SCs in peripheral blood (PERMANOVA p = 0•001). A co-occurrence network analysis showed stool taxa, Erysipelotrichaceae and Blautia, to negatively co-correlate with enriched "death receptor" and "EIF2 signalling" pathways whereas Anaerostipes positively correlated with enriched "interferon signalling", "Nur77 signalling" and "inflammasome" pathways; all of which are host pathways associated with disease severity. In contrast, none of the taxa enriched in SCs correlated with host pathways. INTERPRETATION: TB-specific microbial relationships were identified in oral washes, induced sputum, and stool from cases before the confounding effects of antibiotics. Specific anaerobes in cases' stool predict upregulation of pro-inflammatory immunological pathways, supporting the gut microbiota's role in TB. FUNDING: European & Developing Countries Clinical Trials Partnership, South African-Medical Research Council, National Institute of Allergy and Infectious Diseases

Measurement of the W mass by direct reconstruction in e+e−e^+ e^- collisions at 172 GeV

The mass of the W boson is obtained from reconstructed invariant mass distributions in W-pair events. The sample of W pairs is selected from 10.65~pb$^{-1}$ collected with the ALEPH detector at a mean centre-of-mass energy of 172.09 \GEV. The invariant mass distribution of simulated events are fitted to the experimental distributions and the following W masses are obtained: $WW \to q\overline{q}q\overline{q } m_W = 81.30 +- 0.47(stat.) +- 0.11(syst.) GeV/c^2$, $WW \to l\nu q\overline{q}(l=e,\mu) m_W = 80.54 +- 0.47(stat.) +- 0.11(syst.) GeV/c^2$, $WW \to \tau\nu q\overline{q} m_W = 79.56 +- 1.08(stat.) +- 0.23(syst.) GeV/C62$. The statistical errors are the expected errors for Monte Carlo samples of the same integrated luminosity as the data. The combination of these measurements gives: $m_W = 80.80 +- 0.11(syst.) +- 0.03(LEP energy) GeV/^2$

Relevance of Bcl-x expression in different types of endometrial tissues

<p>Abstract</p> <p>Objectives</p> <p>To explore the roles of Bcl-xl and Bcl-xs in the development and progression of endometrial carcinoma, and to analyze the correlation between Bcl-xl and Bcl-xs.</p> <p>Methods</p> <p>RT-PCR and Western-blot assay were applied to detect the expressions of Bcl-xl and Bcl-xs in endometrial tissues of various histomorphologic types.</p> <p>Results</p> <p>The Bcl-xl expression levels of simple and atypical hyperplasia endometrial tissues were not significantly different from that of normal endometrial tissue (both <it>P </it>> 0.05). On contrary, Bcl-xl expression in endometrial carcinoma tissue was significantly higher than the normal endometrial tissue (<it>P </it>= 0.00), which was correlated with the pathological grading of endometrial carcinoma (F = 5.33, <it>P </it>= 0.02). In addition, Bcl-xs mRNA level in simple hyperplasia endometrial tissue had no significant difference compared to that in normal endometrial tissue (<it>P </it>= 0.12), while the levels of atypical hyperplasia and endometrial carcinoma endometrial tissues were significantly different from the normal endometrial tissue (both <it>P </it>= 0.00). Furthermore, level of Bcl-xs mRNA was correlated with the clinical staging and lymph node metastasis of the endometrial carcinoma (<it>P </it>< 0.05). The expressions of Bcl-xl and Bcl-xs were negatively correlated with each other (<it>r </it>= -0.76).</p> <p>Conclusion</p> <p>The abnormal expressions of Bcl-xs and Bcl-xl were one of the molecular mechanisms for the pathogenesis of endometrial carcinoma, and altered ratio between these two might involve in the onset of endometrial carcinoma.</p

A reference frame for blood volume in children and adolescents

BACKGROUND: Our primary purpose was to determine the normal range and variability of blood volume (BV) in healthy children, in order to provide reference values during childhood and adolescence. Our secondary aim was to correlate these vascular volumes to body size parameters and pubertal stages, in order to determine the best normalisation parameter. METHODS: Plasma volume (PV) and red cell volume (RCV) were measured and F-cell ratio was calculated in 77 children with idiopathic nephrotic syndrome in drug-free remission (mean age, 9.8 ± 4.6 y). BV was calculated as the sum of PV and RCV. Due to the dependence of these values on age, size and sex, all data were normalised for body size parameters. RESULTS: BV normalised for lean body mass (LBM) did not differ significantly by sex (p < 0.376) or pubertal stage (p < 0.180), in contrast to normalisation for the other anthropometric parameters. There was no significant difference between reference values for children and adults. CONCLUSION: LBM was the anthropometric index most closely correlated to vascular fluid volumes, independent of age, gender and pubertal stage