How Does the dGEMRIC Index Change After Surgical Treatment for FAI? A Prospective Controlled Study: Preliminary Results.

BACKGROUND Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) allows an objective, noninvasive, and longitudinal quantification of biochemical cartilage properties. Although dGEMRIC has been used to monitor the course of cartilage degeneration after periacetabular osteotomy (PAO) for correction of hip dysplasia, such longitudinal data are currently lacking for femoroacetabular impingement (FAI). QUESTIONS/PURPOSES (1) How does the mean acetabular and femoral dGEMRIC index change after surgery for FAI at 1-year followup compared with a similar group of patients with FAI treated without surgery? (2) Does the regional distribution of the acetabular and femoral dGEMRIC index change for the two groups over time? (3) Is there a correlation between the baseline dGEMRIC index and the change of patient-reported outcome measures (PROMs) at 1-year followup? (4) Among those treated surgically, can dGEMRIC indices distinguish between intact and degenerated cartilage? METHODS We performed a prospective, comparative, nonrandomized, longitudinal study. At the time of enrollment, the patients' decision whether to undergo surgery or choose nonoperative treatment was not made yet. Thirty-nine patients (40 hips) who underwent either joint-preserving surgery for FAI (20 hips) or nonoperative treatment (20 hips) were included. The two groups did not differ regarding Tönnis osteoarthritis score, preoperative PROMs, or baseline dGEMRIC indices. There were more women (60% versus 30%, p = 0.003) in the nonoperative group and patients were older (36 ± 8 years versus 30 ± 8 years, p = 0.026) and had lower alpha angles (65° ± 10° versus 73° ± 12°, p = 0.022) compared with the operative group. We used a 3.0-T scanner and a three-dimensional dual flip-angle gradient-echo technique for the dGEMRIC technique for the baseline and the 1-year followup measurements. dGEMRIC indices of femoral and acetabular cartilage were measured separately on the initial and followup radial dGEMRIC reformats in direct comparison with morphologic radial images. Regions of interest were placed manually peripherally and centrally within the cartilage based on anatomic landmarks at the clockface positions. The WOMAC, the Hip disability and Osteoarthritis Outcome Score, and the modified Harris hip score were used as PROMs. Among those treated surgically, the intraoperative damage according to the Beck grading was recorded and compared with the baseline dGEMRIC indices. RESULTS Although both the operative and the nonoperative groups experienced decreased dGEMRIC indices, the declines were more pronounced in the operative group (-96 ± 112 ms versus -16 ± 101 ms on the acetabular side and -96 ± 123 ms versus -21 ± 83 ms on the femoral side in the operative and nonoperative groups, respectively; p < 0.001 for both). Patients undergoing hip arthroscopy and surgical hip dislocation experienced decreased dGEMRIC indices; the decline in femoral dGEMRIC indices was more pronounced in hips after surgical hip dislocation (-120 ± 137 ms versus -61 ± 89 ms, p = 0.002). In the operative group a decline in dGEMRIC indices was observed in 43 of 44 regions over time. In the nonoperative group a decline in dGEMRIC indices was observed in four of 44 regions over time. The strongest correlation among patients treated surgically was found between the change in WOMAC and baseline dGEMRIC indices for the entire joint (R = 0.788, p < 0.001). Among those treated nonoperatively, no correlation between baseline dGEMRIC indices and change in PROMs was found. In the posterosuperior quadrant, the dGEMRIC index was higher for patients with intact cartilage compared with hips with chondral lesions (592 ± 203 ms versus 444 ± 205 ms, p < 0.001). CONCLUSIONS We found a decline in acetabular, femoral, and regional dGEMRIC indices for the surgically treated group at 1-year followup despite an improvement in all PROMs. We observed a similar but less pronounced decrease in the dGEMRIC index in symptomatic patients without surgical treatment indicating continuous cartilage degeneration. Although treatment of FAI is intended to alter the forces acting across the hip by eliminating impingement, its effects on cartilage biology are not clear. dGEMRIC provides a noninvasive method of assessing these effects. Longer term studies will be needed to determine whether the matrix changes of the bradytrophic cartilage seen here are permanent or clinically important. LEVEL OF EVIDENCE Level II, therapeutic study

[Impingement of the hip].

Femoroacetabular impingement (FAI) describes the repetitive painful contact between the acetabulum, the pelvis and the proximal femur. This bony abutment can lead to a characteristic pattern of chondrolabral damage and is one of the main etiological factors in the development of juvenile osteoarthritis of the hip joint. This article describes the current treatment concepts of FAI and the radiological assessment including an overview of standard measurement methods, coxometric parameters and cut-off values. Furthermore, the authors stress the importance of a profound understanding of the entire configuration of the pelvis and the dynamic interplay of its components

Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study

Introduction: Guidelines recommend that two blood cultures be performed in patients with febrile urinary tract infection (UTI), to detect bacteremia and help diagnose urosepsis. The usefulness and cost-effectiveness of this practice have been criticized. This study aimed to evaluate clinical characteristics and the biomarker procalcitonin (PCT) as an aid in predicting bacteremia. Methods: A prospective observational multicenter cohort study included consecutive adults with febrile UTI in 35 primary care units and 8 emergency departments of 7 regional hospitals. Clinical and microbiological data were collected and PCT and time to positivity (TTP) of blood culture were measured. Results: Of 581 evaluable patients, 136 (23%) had bacteremia. The median age was 66 years (interquartile range 46 to 78 years) and 219 (38%) were male. We evaluated three different models: a clinical model including seven bedside characteristics, the clinical model plus PCT, and a PCT only model. The diagnostic abilities of these models as reflected by area under the curve of the receiver operating characteristic were 0.71 (95% confidence interval (CI): 0.66 to 0.76), 0.79 (95% CI: 0.75 to 0.83) and 0.73 (95% CI: 0.68 to 0.77) respectively. Calculating corresponding sensitivity and specificity for the presence of bacteremia after each step of adding a significant predictor in the model yielded that the PCT > 0.25 mu g/l only model had the best diagnostic performance (sensitivity 0.95; 95% CI: 0.89 to 0.98, specificity 0.50; 95% CI: 0.46 to 0.55). Using PCT as a single decision tool, this would result in 40% fewer blood cultures being taken, while still identifying 94 to 99% of patients with bacteremia. The TTP of E. coli positive blood cultures was linearly correlated with the PCT log value; the higher the PCT the shorter the TTP (R-2 = 0.278, P = 0.007). Conclusions: PCT accurately predicts the presence of bacteremia and bacterial load in patients with febrile UTI. This may be a helpful biomarker to limit use of blood culture resources.Immunogenetics and cellular immunology of bacterial infectious disease

Design and Pre-Clinical Evaluation of a Universal HIV-1 Vaccine

BACKGROUND: One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test. METHODOLOGY AND FINDINGS: To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIV(CONSV) protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8(+) and CD4(+) T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection. SIGNIFICANCE: Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity

Heroes and villains of world history across cultures

© 2015 Hanke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedEmergent properties of global political culture were examined using data from the World History Survey (WHS) involving 6,902 university students in 37 countries evaluating 40 figures from world history. Multidimensional scaling and factor analysis techniques found only limited forms of universality in evaluations across Western, Catholic/Orthodox, Muslim, and Asian country clusters. The highest consensus across cultures involved scientific innovators, with Einstein having the most positive evaluation overall. Peaceful humanitarians like Mother Theresa and Gandhi followed. There was much less cross-cultural consistency in the evaluation of negative figures, led by Hitler, Osama bin Laden, and Saddam Hussein. After more traditional empirical methods (e.g., factor analysis) failed to identify meaningful cross-cultural patterns, Latent Profile Analysis (LPA) was used to identify four global representational profiles: Secular and Religious Idealists were overwhelmingly prevalent in Christian countries, and Political Realists were common in Muslim and Asian countries. We discuss possible consequences and interpretations of these different representational profiles.This research was supported by grant RG016-P-10 from the Chiang Ching-Kuo Foundation for International Scholarly Exchange (http://www.cckf.org.tw/). Religion Culture Entropy China Democracy Economic histor

Dual Neonate Vaccine Platform against HIV-1 and M. tuberculosis

Acquired immunodeficiency syndrome and tuberculosis (TB) are two of the world's most devastating diseases. The first vaccine the majority of infants born in Africa receive is Mycobacterium bovis bacillus Calmette-Guérin (BCG) as a prevention against TB. BCG protects against disseminated disease in the first 10 years of life, but provides a variable protection against pulmonary TB and enhancing boost delivered by recombinant modified vaccinia virus Ankara (rMVA) expressing antigen 85A (Ag85A) of M. tuberculosis is currently in phase IIb evaluation in African neonates. If the newborn's mother is positive for human immunodeficiency virus type 1 (HIV-1), the baby is at high risk of acquiring HIV-1 through breastfeeding. We suggested that a vaccination consisting of recombinant BCG expressing HIV-1 immunogen administered at birth followed by a boost with rMVA sharing the same immunogen could serve as a strategy for prevention of mother-to-child transmission of HIV-1 and rMVA expressing an African HIV-1-derived immunogen HIVA is currently in phase I trials in African neonates. Here, we aim to develop a dual neonate vaccine platform against HIV-1 and TB consisting of BCG.HIVA administered at birth followed by a boost with MVA.HIVA.85A. Thus, mMVA.HIVA.85A and sMVA.HIVA.85A vaccines were constructed, in which the transgene transcription is driven by either modified H5 or short synthetic promoters, respectively, and tested for immunogenicity alone and in combination with BCG.HIVA222. mMVA.HIVA.85A was produced markerless and thus suitable for clinical manufacture. While sMVA.HIVA.85A expressed higher levels of the immunogens, it was less immunogenic than mMVA.HIVA.85A in BALB/c mice. A BCG.HIVA222–mMVA.HIVA.85A prime-boost regimen induced robust T cell responses to both HIV-1 and M. tuberculosis. Therefore, proof-of-principle for a dual anti-HIV-1/M. tuberculosis infant vaccine platform is established. Induction of immune responses against these pathogens soon after birth is highly desirable and may provide a basis for lifetime protection maintained by boosts later in life

Protective Efficacy of Serially Up-Ranked Subdominant CD8+ T Cell Epitopes against Virus Challenges

Immunodominance in T cell responses to complex antigens like viruses is still incompletely understood. Some data indicate that the dominant responses to viruses are not necessarily the most protective, while other data imply that dominant responses are the most important. The issue is of considerable importance to the rational design of vaccines, particularly against variable escaping viruses like human immunodeficiency virus type 1 and hepatitis C virus. Here, we showed that sequential inactivation of dominant epitopes up-ranks the remaining subdominant determinants. Importantly, we demonstrated that subdominant epitopes can induce robust responses and protect against whole viruses if they are allowed at least once in the vaccination regimen to locally or temporally dominate T cell induction. Therefore, refocusing T cell immune responses away from highly variable determinants recognized during natural virus infection towards subdominant, but conserved regions is possible and merits evaluation in humans

Prevalence of maternal smoking and environmental tobacco smoke exposure during pregnancy and impact on birth weight: retrospective study using Millennium Cohort

<p>Abstract</p> <p>Background</p> <p>Meta-analyses of studies investigating the impact of maternal environmental tobacco smoke (ETS) on birth weight have not produced robust findings. Although, ante natal ETS exposure probably reduces infant's birth weights, the scale of this exposure remains unknown. We conducted a large, cohort study to assess the impact of ETS exposure on birth weight whilst adjusting for the many factors known to influence this.</p> <p>Method</p> <p>Retrospective study using interview data from parents of 18,297 children born in 2000/2001 and living in the UK 9 months afterwards (the Millennium Cohort Survey). Comparison of birth weight, sex and gestational age specific (SGA) z score, birth before 37 weeks and birth weight < 2.5 Kg (LBW) in infants born to women exposed to: i) no tobacco smoke, ii) ETS only and iii) maternal smoking whilst pregnant.</p> <p>Results</p> <p>13% of UK infants were exposed to ETS and 36% to maternal smoking ante natally. Compared to no ante natal tobacco smoke exposure, domestic ETS lowered infants' adjusted mean birth weights by 36 g (95% CI, 5 g to 67 g) and this effect showed a dose-response relationship. ETS exposure also caused non-significant increases in the adjusted risks of Low Birth Weight (<2.5 Kg) [OR 1.23 (95% CI, 0.96 to 1.58) and premature birth [OR 1.21 (95% CI, 0.96 to 1.51)], whilst the impacts of maternal smoking were greater and statistically significant.</p> <p>Conclusion</p> <p>UK prevalences of domestic ETS exposure and maternal smoking in pregnancy remain high and ETS exposure lowers infants' birth weights.</p

Platelet Function in Stored Heparinised Autologous Blood Is Not Superior to in Patient Platelet Function during Routine Cardiopulmonary Bypass

Background: In cardiac surgery, cardiopulmonary bypass (CPB) and unfractionated heparin have negative effects on blood platelet function. In acute normovolemic haemodilution autologous unfractionated heparinised blood is stored ex-vivo and retransfused at the end of the procedure to reduce (allogeneic) transfusion requirements. In this observational study we assessed whether platelet function is better preserved in ex vivo stored autologous blood compared to platelet function in the patient during CPB. Methodology/Principal Finding: We measured platelet aggregation responses pre-CPB, 5 min after the start of CPB, at the end of CPB, and after unfractionated heparin reversal, using multiple electrode aggregometry (MultiplateH) with adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) and ristocetin activated test cells. We compared blood samples taken from the patient with samples taken from 100 ml ex-vivo stored blood, which we took to mimick blood storage during normovolemic haemodilution. Platelet function declined both in ex-vivo stored blood as well as in blood taken from the patient. At the end of CPB there were no differences in platelet aggregation responses between samples from the ex vivo stored blood and the patient. Conclusion/Significance: Ex vivo preservation of autologous blood in unfractionated heparin does not seem to b