Feasibility of the STarT back screening tool in chiropractic clinics: a cross-sectional study of patients with low back pain

The STarT back screening tool (SBT) allocates low back pain (LBP) patients into three risk groups and is intended to assist clinicians in their decisions about choice of treatment. The tool consists of domains from larger questionnaires that previously have been shown to be predictive of non-recovery from LBP. This study was performed to describe the distribution of depression, fear avoidance and catastrophising in relation to the SBT risk groups. A total of 475 primary care patients were included from 19 chiropractic clinics. They completed the SBT, the Major Depression Inventory (MDI), the Fear Avoidance Beliefs Questionnaire (FABQ), and the Coping Strategies Questionnaire. Associations between the continuous scores of the psychological questionnaires and the SBT were tested by means of linear regression, and the diagnostic performance of the SBT in relation to the other questionnaires was described in terms of sensitivity, specificity and likelihood ratios

Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: Different boosting intervals and implications for efficacy trials

Objectives. To investigate the safety and immunogenicity of boosting BCG with modified vaccinia Ankara expressing antigen 85A (MVA85A), shortly after BCG vaccination, and to compare this first with the immunogenicity of BCG vaccination alone and second with a previous clinical trial where MVA85A was administered more than 10 years after BCG vaccination. Design. There are two clinical trials reported here: a Phase I observational trial with MVA85A; and a Phase IV observational trial with BCG. These clinical trials were all conducted in the UK in healthy, HIV negative, BCG naı¨ve adults. Subjects were vaccinated with BCG alone; or BCG and then subsequently boosted with MVA85A four weeks later (short interval). The outcome measures, safety and immunogenicity, were monitored for six months. The immunogenicity results from this short interval BCG prime–MVA85A boost trial were compared first with the BCG alone trial and second with a previous clinical trial where MVA85A vaccination was administered many years after vaccination with BCG. Results. MVA85A was safe and highly immunogenic when administered to subjects who had recently received BCG vaccination. When the short interval trial data presented here were compared with the previous long interval trial data, there were no significant differences in the magnitude of immune responses generated when MVA85A was administered shortly after, or many years after BCG vaccination. Conclusions. The clinical trial data presented here provides further evidence of the ability of MVA85A to boost BCG primed immune responses. This boosting potential is not influenced by the time interval between prior BCG vaccination and boosting with MVA85A. These findings have important implications for the design of efficacy trials with MVA85A. Boosting BCG induced anti-mycobacterial immunity in either infancy or adolescence are both potential applications for this vaccine, given the immunological data presented here. Trial Registration. ClinicalTrials.Oxford University was the sponsor for all the clinical trials reported here

Natural variation in immune responses to neonatal mycobacterium bovis bacillus calmette-guerin (BCG) vaccination in a cohort of Gambian infants

Background There is a need for new vaccines for tuberculosis (TB) that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-) is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN- responses to BCG in this age group are poorly described. Characterisation of IFN- responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. Methodology/Principal Findings 236 healthy Gambian babies were vaccinated with M. bovis BCG at birth. IFN-, interleukin (IL)-5 and IL-13 responses to purified protein derivative (PPD), killed Mycobacterium tuberculosis (KMTB), M. tuberculosis short term culture filtrate (STCF) and M. bovis BCG antigen 85 complex (Ag85) were measured in a whole blood assay two months after vaccination. Cytokine responses varied up to 10 log-fold within this population. The majority of infants (89-98% depending on the antigen) made IFN- responses and there was significant correlation between IFN- responses to the different mycobacterial antigens (Spearman’s coefficient ranged from 0.340 to 0.675, p=10-6-10-22). IL-13 and IL-5 responses were generally low and there were more non-responders (33-75%) for these cytokines. Nonetheless, significant correlations were observed for IL-13 and IL-5 responses to different mycobacterial antigens Conclusions/Significance Cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine variation in IFN- responses

Ethanol reversal of tolerance to the respiratory depressant effects of morphine

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths

Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes.

Multi-nucleotide variants (MNVs), defined as two or more nearby variants existing on the same haplotype in an individual, are a clinically and biologically important class of genetic variation. However, existing tools typically do not accurately classify MNVs, and understanding of their mutational origins remains limited. Here, we systematically survey MNVs in 125,748 whole exomes and 15,708 whole genomes from the Genome Aggregation Database (gnomAD). We identify 1,792,248 MNVs across the genome with constituent variants falling within 2 bp distance of one another, including 18,756 variants with a novel combined effect on protein sequence. Finally, we estimate the relative impact of known mutational mechanisms - CpG deamination, replication error by polymerase zeta, and polymerase slippage at repeat junctions - on the generation of MNVs. Our results demonstrate the value of haplotype-aware variant annotation, and refine our understanding of genome-wide mutational mechanisms of MNVs

Ferroelectricity induced by interatomic magnetic exchange interaction

Multiferroics, where two or more ferroic order parameters coexist, is one of the hottest fields in condensed matter physics and materials science[1-9]. However, the coexistence of magnetism and conventional ferroelectricity is physically unfavoured[10]. Recently several remedies have been proposed, e.g., improper ferroelectricity induced by specific magnetic[6] or charge orders[2]. Guiding by these theories, currently most research is focused on frustrated magnets, which usually have complicated magnetic structure and low magnetic ordering temperature, consequently far from the practical application. Simple collinear magnets, which can have high magnetic transition temperature, have never been considered seriously as the candidates for multiferroics. Here, we argue that actually simple interatomic magnetic exchange interaction already contains a driving force for ferroelectricity, thus providing a new microscopic mechanism for the coexistence and strong coupling between ferroelectricity and magnetism. We demonstrate this mechanism by showing that even the simplest antiferromagnetic (AFM) insulator MnO, can display a magnetically induced ferroelectricity under a biaxial strain

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

Measuring educational needs among patients with rheumatoid arthritis using the Dutch version of the Educational Needs Assessment Tool (DENAT)

The Educational Needs Assessment Tool (ENAT) was developed in the United Kingdom (UK) to systematically assess the educational needs of patients with arthritis. The aim of the present study was to describe the educational needs of Dutch patients with rheumatoid arthritis (RA) by using the Dutch version of the ENAT (DENAT). The original UK version of the ENAT, comprising 39 items grouped into seven domains, was translated into Dutch according to international guidelines for cross-cultural translation and adaptation. The DENAT was then sent to a random sample of 319 RA patients registered at the outpatient clinic of a university hospital. For each domain (score range 1–5, equalling low–high educational needs), a median score with the inter-quartile range was computed. The Kruskal–Wallis test was used to determine possible associations between educational needs and age, disease duration, gender and educational background. The response rate was 165 out of 319 (52%). The median educational needs scores were 2.5 for “managing pain”, 3.0 for “movement”, 2.0 for “feelings”, 4.0 for “arthritis process”, 4.0 for “treatments from health professionals”, 3.5 for “self-help measures” and 2.5 for “support systems”. Lower age and shorter disease duration were associated with more educational needs in the domain “support systems”. In addition, younger patients had more educational needs regarding managing pain and feelings than older patients. There were no associations between gender or educational background and educational needs. The DENAT has demonstrated its ability to identify individual educational needs of Dutch patients with RA. The lower age and shorter disease duration were associated with more educational needs. The practical applicability of the DENAT needs further research