Translation, adaptation and validation of the Roland-Morris questionnaire - Brazil Roland-Morris

The purpose of the present study was to translate the Roland-Morris (RM) questionnaire into Brazilian-Portuguese and adapt and validate it. First 3 English teachers independently translated the original questionnaire into Brazilian-Portuguese and a consensus version was generated. Later, 3 other translators, blind to the original questionnaire, performed a back translation. This version was then compared with the original English questionnaire. Discrepancies were discussed and solved by a panel of 3 rheumatologists and the final Brazilian version was established (Brazil-RM). This version was then pretested on 30 chronic low back pain patients consecutively selected from the spine disorders outpatient clinic. In addition to the traditional clinical outcome measures, the Brazil-RM, a 6-point pain scale (from no pain to unbearable pain), and its numerical pain rating scale (PS) (0 to 5) and a visual analog scale (VAS) (0 to 10) were administered twice by one interviewer (1 week apart) and once by one independent interviewer. Spearman's correlation coefficient (SCC) and intraclass correlation coefficient (ICC) were computed to assess test-retest and interobserver reliability. Cross-sectional construct validity was evaluated using the SCC. In the pretesting session, all questions were well understood by the patients. The mean time of questionnaire administration was 4 min and 53 s. The SCC and ICC were 0.88 (P<0.01) and 0.94, respectively, for the test-retest reliability and 0.86 (P<0.01) and 0.95, respectively, for interobserver reliability. The correlation coefficient was 0.80 (P<0.01) between the PS and Brazil-RM score and 0.79 (P<0.01) between the VAS and Brazil-RM score. We conclude that the Brazil-RM was successfully translated and adapted for application to Brazilian patients, with satisfactory reliability and cross-sectional construct validity.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de ReumatologiaUNIFESP, EPM, Disciplina de ReumatologiaSciEL

Early Epstein-Barr Virus Genomic Diversity and Convergence toward the B95.8 Genome in Primary Infection

Over 90% of the world\u27s population is persistently infected with Epstein-Barr virus. While EBV does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (AIM) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. At present, very few primary, circulating EBV genomes have been sequenced directly from infected individuals. While low levels of diversity and low viral evolution rates have been predicted for double-stranded DNA (dsDNA) viruses, recent studies have demonstrated appreciable diversity in common dsDNA pathogens (e.g., cytomegalovirus). Here, we report 40 full-length EBV genome sequences obtained from matched oral wash and B cell fractions from a cohort of 10 AIM patients. Both intra- and interpatient diversity were observed across the length of the entire viral genome. Diversity was most pronounced in viral genes required for establishing latent infection and persistence, with appreciable levels of diversity also detected in structural genes, including envelope glycoproteins. Interestingly, intrapatient diversity declined significantly over time (P \u3c 0.01), and this was particularly evident on comparison of viral genomes sequenced from B cell fractions in early primary infection and convalescence (P \u3c 0.001). B cell-associated viral genomes were observed to converge, becoming nearly identical to the B95.8 reference genome over time (Spearman rank-order correlation test; r = -0.5589, P = 0.0264). The reduction in diversity was most marked in the EBV latency genes. In summary, our data suggest independent convergence of diverse viral genome sequences toward a reference-like strain within a relatively short period following primary EBV infection. IMPORTANCE Identification of viral proteins with low variability and high immunogenicity is important for the development of a protective vaccine. Knowledge of genome diversity within circulating viral populations is a key step in this process, as is the expansion of intrahost genomic variation during infection. We report full-length EBV genomes sequenced from the blood and oral wash of 10 individuals early in primary infection and during convalescence. Our data demonstrate considerable diversity within the pool of circulating EBV strains, as well as within individual patients. Overall viral diversity decreased from early to persistent infection, particularly in latently infected B cells, which serve as the viral reservoir. Reduction in B cell-associated viral genome diversity coincided with a convergence toward a reference-like EBV genotype. Greater convergence positively correlated with time after infection, suggesting that the reference-like genome is the result of selection

Development of an Accepted Medical Condition List for Mars Transit Medical Capability Scoping

No abstract availabl

Cultivated Vaginal Microbiomes Alter HIV-1 Infection and Antiretroviral Efficacy in Colonized Epithelial Multilayer Cultures

There is a pressing need for modeling of the symbiotic and at times dysbiotic relationship established between bacterial microbiomes and human mucosal surfaces. In particular clinical studies have indicated that the complex vaginal microbiome (VMB) contributes to the protection against sexually-transmitted pathogens including the life-threatening human immunodeficiency virus (HIV-1). The human microbiome project has substantially increased our understanding of the complex bacterial communities in the vagina however, as is the case for most microbiomes, very few of the community member species have been successfully cultivated in the laboratory limiting the types of studies that can be completed. A genetically controlled ex vivo model system is critically needed to study the complex interactions and associated molecular dialog. We present the first vaginal mucosal culture model that supports colonization by both healthy and dysbiotic VMB from vaginal swabs collected from routine gynecological patients. The immortalized vaginal epithelial cells used in the model and VMB cryopreservation methods provide the opportunity to reproducibly create replicates for lab-based evaluations of this important mucosal/bacterial community interface. The culture system also contains HIV-1 susceptible cells allowing us to study the impact of representative microbiomes on replication. Our results show that our culture system supports stable and reproducible colonization by VMB representing distinct community state types and that the selected representatives have significantly different effects on the replication of HIV-1. Further, we show the utility of the system to predict unwanted alterations in efficacy or bacterial community profiles following topical application of a front line antiretroviral

Law of Genome Evolution Direction : Coding Information Quantity Grows

The problem of the directionality of genome evolution is studied. Based on the analysis of C-value paradox and the evolution of genome size we propose that the function-coding information quantity of a genome always grows in the course of evolution through sequence duplication, expansion of code, and gene transfer from outside. The function-coding information quantity of a genome consists of two parts, p-coding information quantity which encodes functional protein and n-coding information quantity which encodes other functional elements except amino acid sequence. The evidences on the evolutionary law about the function-coding information quantity are listed. The needs of function is the motive force for the expansion of coding information quantity and the information quantity expansion is the way to make functional innovation and extension for a species. So, the increase of coding information quantity of a genome is a measure of the acquired new function and it determines the directionality of genome evolution.Comment: 16 page

Effect of formant frequency spacing on perceived gender in pre-pubertal children's voices

<div><p>Background</p><p>It is usually possible to identify the sex of a pre-pubertal child from their voice, despite the absence of sex differences in fundamental frequency at these ages. While it has been suggested that the overall spacing between formants (formant frequency spacing - ΔF) is a key component of the expression and perception of sex in children's voices, the effect of its continuous variation on sex and gender attribution has not yet been investigated.</p><p>Methodology/Principal findings</p><p>In the present study we manipulated voice ΔF of eight year olds (two boys and two girls) along continua covering the observed variation of this parameter in pre-pubertal voices, and assessed the effect of this variation on adult ratings of speakers' sex and gender in two separate experiments. In the first experiment (sex identification) adults were asked to categorise the voice as either male or female. The resulting identification function exhibited a gradual slope from male to female voice categories. In the second experiment (gender rating), adults rated the voices on a continuum from “masculine boy” to “feminine girl”, gradually decreasing their masculinity ratings as ΔF increased.</p><p>Conclusions/Significance</p><p>These results indicate that the role of ΔF in voice gender perception, which has been reported in adult voices, extends to pre-pubertal children's voices: variation in ΔF not only affects the perceived sex, but also the perceived masculinity or femininity of the speaker. We discuss the implications of these observations for the expression and perception of gender in children's voices given the absence of anatomical dimorphism in overall vocal tract length before puberty.</p></div

Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements

Physical interactions between genetic elements located throughout the genome play important roles in gene regulation and can be identified with the Chromosome Conformation Capture (3C) methodology. 3C converts physical chromatin interactions into specific ligation products, which are quantified individually by PCR. Here we present a high-throughput 3C approach, 3C-Carbon Copy (5C), that employs microarrays or quantitative DNA sequencing using 454-technology as detection methods. We applied 5C to analyze a 400-kb region containing the human beta-globin locus and a 100-kb conserved gene desert region. We validated 5C by detection of several previously identified looping interactions in the beta-globin locus. We also identified a new looping interaction in K562 cells between the beta-globin Locus Control Region and the gamma-beta-globin intergenic region. Interestingly, this region has been implicated in the control of developmental globin gene switching. 5C should be widely applicable for large-scale mapping of cis- and trans- interaction networks of genomic elements and for the study of higher-order chromosome structure

Boosting Long-term Memory via Wakeful Rest: Intentional Rehearsal is not Necessary, Automatic Consolidation is Sufficient.

<div><p>People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as ‘foreign names in a bridge club abroad’ and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is <i>not</i> dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is <i>sufficient</i> for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.</p></div

The immune cell landscape in kidneys of patients with lupus nephritis.

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies