Bilateral pedicle stress fracture in the lumbar spine of a sedentary office worker

A case of bilateral pedicle fracture in the lumbar spine of a sedentary office worker is being presented. No such case has been reported in the literature previously. Bilateral pedicle fracture is a rare entity. Few cases have been reported in literature. All the reported cases had some underlying causative factors like degenerative spine disease, previous spinal surgery or stress-related activities, e.g. athletes. Our case is a 36-year-old sedentary office worker with none of the factors mentioned. We present a case of a 36-year-old sedentary worker with long-standing low backache. There were no root tension signs. Plain radiographs were inconclusive. The patient had a CT scan. The CT scan revealed long-standing defects in the pedicles of L2 vertebra with pseudoarthrosis. Infiltration with anaesthetic relieved the symptoms. Our patient was managed conservatively with spine rehabilitation physiotherapy program. Pedicle fracture can develop due to abnormal stresses in the pedicle either because of previous spinal surgery or spondylitic changes in the spine. Bilateral pedicle fracture in the absence of these conditions is extremely rare

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

Unearthing how, why, for whom and under what health system conditions the antiretroviral treatment adherence club intervention in South Africa works: A realist theory refining approach

BACKGROUND: Poor retention in care and suboptimal adherence to antiretroviral treatment (ART) undermine its successful rollout in South Africa. The adherence club intervention was designed as an adherence-enhancing intervention to enhance the retention in care of patients on ART and their adherence to medication. Although empirical evidence suggests the effective superiority of the adherence club intervention to standard clinic ART care schemes, it is poorly understood exactly how and why it works, and under what health system contexts. To this end, we aimed to develop a refined programme theory explicating how, why, for whom and under what health system contexts the adherence club intervention works (or not). METHODS: We undertook a realist evaluation study to uncover the programme theory of the adherence club intervention. We elicited an initial programme theory of the adherence club intervention and tested the initial programme theory in three contrastive sites. Using a cross-case analysis approach, we delineated the conceptualisation of the intervention, context, actor and mechanism components of the three contrastive cases to explain the outcomes of the adherence club intervention, guided by retroductive inferencing. RESULTS: We found that an intervention that groups clinically stable patients on ART in a convenient space to receive a quick and uninterrupted supply of medication, health talks, counselling, and immediate access to a clinician when required works because patients’ self-efficacy improves and they become motivated and nudged to remain in care and adhere to medication. The successful implementation and rollout of the adherence club intervention are contingent on the separation of the adherence club programme from other patients who are HIV-negative. In addition, there should be available convenient space for the adherence club meetings, continuous support of the adherence club facilitators by clinicians and buy-in from the health workers at the health-care facility and the community. CONCLUSION: Understanding what aspects of antiretroviral club intervention works, for what sections of the patient population, and under which community and health systems contexts, could inform guidelines for effective implementation in different contexts and scaling up of the intervention to improve population-level ART adherence

A realist approach to eliciting the initial programme theory of the antiretroviral treatment adherence club intervention in the Western Cape Province, South Africa

BACKGROUND: The successful initiation of people living with HIV/AIDS on antiretroviral therapy (ART) in South Africa has engendered challenges of poor retention in care and suboptimal adherence to medication. The adherence club intervention was implemented in the Metropolitan area of the Western Cape Province to address these challenges. The adherence club programme has shown potential to relieve clinic congestion, improve retention in care and enhance treatment adherence in the context of rapidly growing HIV patient populations being initiated on ART. Nevertheless, how and why the adherence club intervention works is not clearly understood. We aimed to elicit an initial programme theory as the first phase of the realist evaluation of the adherence club intervention in the Western Cape Province. METHODS: The realist evaluation approach guided the elicitation study. First, information was obtained from an exploratory qualitative study of programme designers’ and managers’ assumptions of the intervention. Second, a document review of the design, rollout, implementation and outcome of the adherence clubs followed. Third, a systematic review of available studies on group-based ART adherence support models in Sub-Saharan Africa was done, and finally, a scoping review of social, cognitive and behavioural theories that have been applied to explain adherence to ART. We used the realist evaluation heuristic tool (Intervention-context-actors-mechanism-outcome) to synthesise information from the sources into a configurational map. The configurational mapping, alignment of a specific combination of attributes, was based on the generative causality logic – retroduction. RESULTS: We identified two alternative theories: The first theory supposes that patients become encouraged, empowered and motivated, through the adherence club intervention to remain in care and adhere to the treatment. The second theory suggests that stable patients on ART are being nudged through club rules and regulations to remain in care and adhere to the treatment with the goal to decongest the primary health care facilities. CONCLUSION: The initial programme theory describes how (dynamics) and why (theories) the adherence club intervention is expected to work. By testing theories in “real intervention cases” using the realist evaluation approach, the theories can be modified, refuted and/or reconstructed to elicit a refined theory of how and why the adherence club intervention works

Contribution of Various Carbon Sources Toward Isoprene Biosynthesis in Poplar Leaves Mediated by Altered Atmospheric CO2 Concentrations

Biogenically released isoprene plays important roles in both tropospheric photochemistry and plant metabolism. We performed a 13CO2-labeling study using proton-transfer-reaction mass spectrometry (PTR-MS) to examine the kinetics of recently assimilated photosynthate into isoprene emitted from poplar (Populus × canescens) trees grown and measured at different atmospheric CO2 concentrations. This is the first study to explicitly consider the effects of altered atmospheric CO2 concentration on carbon partitioning to isoprene biosynthesis. We studied changes in the proportion of labeled carbon as a function of time in two mass fragments, M41+, which represents, in part, substrate derived from pyruvate, and M69+, which represents the whole unlabeled isoprene molecule. We observed a trend of slower 13C incorporation into isoprene carbon derived from pyruvate, consistent with the previously hypothesized origin of chloroplastic pyruvate from cytosolic phosphenolpyruvate (PEP). Trees grown under sub-ambient CO2 (190 ppmv) had rates of isoprene emission and rates of labeling of M41+ and M69+ that were nearly twice those observed in trees grown under elevated CO2 (590 ppmv). However, they also demonstrated the lowest proportion of completely labeled isoprene molecules. These results suggest that under reduced atmospheric CO2 availability, more carbon from stored/older carbon sources is involved in isoprene biosynthesis, and this carbon most likely enters the isoprene biosynthesis pathway through the pyruvate substrate. We offer direct evidence that extra-chloroplastic rather than chloroplastic carbon sources are mobilized to increase the availability of pyruvate required to up-regulate the isoprene biosynthesis pathway when trees are grown under sub-ambient CO2

SAVVY Vaginal Gel (C31G) for Prevention of HIV Infection: A Randomized Controlled Trial in Nigeria

The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk.This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where we enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized 1 ratio 1 to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. We observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9, 3.5). Because of lower-than-expected HIV incidence, we did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use.SAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY

Knowledge gaps and research priorities in tuberculous meningitis [version 1; peer review: 3 approved]

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), accounting for around 1-5% of the global TB caseload, with mortality of approximately 20% in children and up to 60% in persons co-infected with human immunodeficiency virus even in those treated. Relatively few centres of excellence in TBM research exist and the field would therefore benefit from greater co-ordination, advocacy, collaboration and early data sharing. To this end, in 2009, 2015 and 2019 we convened the TBM International Research Consortium, bringing together approximately 50 researchers from five continents. The most recent meeting took place on 1st and 2nd March 2019 in Lucknow, India. During the meeting, researchers and clinicians presented updates in their areas of expertise, and additionally presented on the knowledge gaps and research priorities in that field. Discussion during the meeting was followed by the development, by a core writing group, of a synthesis of knowledge gaps and research priorities within seven domains, namely epidemiology, pathogenesis, diagnosis, antimicrobial therapy, host-directed therapy, critical care and implementation science. These were circulated to the whole consortium for written input and feedback. Further cycles of discussion between the writing group took place to arrive at a consensus series of priorities. This article summarises the consensus reached by the consortium concerning the unmet needs and priorities for future research for this neglected and often fatal disease

Wound contraction effects and antibacterial properties of Tualang honey on full-thickness burn wounds in rats in comparison to hydrofibre

<p>Abstract</p> <p>Background</p> <p>Full-thickness burn wounds require excision and skin grafting. Multiple surgical procedures are inevitable in managing moderate to severe full-thickness burns. Wound bed preparations prior to surgery are necessary in order to prevent wound infection and promote wound healing. Honey can be used to treat burn wounds. However, not all the honey is the same. This study aims to evaluate the wound contraction and antibacterial properties of locally-produced <it>Tualang </it>honey on managing full-thickness burn wounds <it>in vivo</it>.</p> <p>Methods</p> <p>Thirty-six female <it>Sprague Dawley </it>rats were randomly divided into three groups. Under anaesthesia, three full-thickness burn wounds were created on the dorsum of the rats. The full-thickness burn wounds were inoculated with a specific organism (10⁴), namely <it>Pseudomonas aeruginosa </it>(n = 12), <it>Klebsiella pneumoniae </it>(n = 12), or <it>Acinetobacter baumannii </it>(n = 12). The three burn wounds were dressed with <it>Tualang </it>honey, hydrofibre and hydrofibre silver respectively. Swab samples were obtained every 3 days (day 3, 6, 9, 12, 15, 18 and 21) for quantitative and semi-quantitative microbiological analyses. Clinical assessments, including observations concerning the appearance and wound size, were measured at the same time.</p> <p>Results</p> <p>There was a rapid 32.26% reduction in wound size by day 6 (<it>p </it>= 0.008) in the <it>Tualang </it>honey-treated wounds, and 49.27% by day 15 (<it>p </it>= 0.005). The wounds remained smaller by day 18 (<it>p </it>< 0.032). <it>Tualang </it>honey-treated rats demonstrated a reduction in bacterial growth in <it>Pseudomonas aeruginosa </it>inoculated wounds (<it>p </it>= 0.005). However, hydrofibre silver and hydrofibre-treated wounds are superior to honey-treated wounds with <it>Acinetobacter baumannii </it>(<it>p </it>= 0.035). There was no statistical significant of antibacterial property in <it>Klebsiella pneumonia </it>inoculated wounds.</p> <p>Conclusions</p> <p><it>Tualang </it>honey has better results with regards to its control of <it>Pseudomonas aeruginosa </it>and its wound contraction effects on full-thickness burn wound <it>in vivo</it>.</p