Lentiviral Vector Delivery of Human Interleukin-7 (hIL-7) to Human Immune System (HIS) Mice Expands T Lymphocyte Populations

Genetically modified mice carrying engrafted human tissues provide useful models to study human cell biology in physiologically relevant contexts. However, there remain several obstacles limiting the compatibility of human cells within their mouse hosts. Among these is inadequate cross-reactvitiy between certain mouse cytokines and human cellular receptors, depriving the graft of important survival and growth signals. To circumvent this problem, we utilized a lentivirus-based delivery system to express physiologically relevant levels of human interleukin-7 (hIL-7) in Rag2-/-γc-/- mice following a single intravenous injection. hIL-7 promoted homeostatic proliferation of both adoptively transferred and endogenously generated T-cells in Rag2-/-γc-/- Human Immune System (HIS) mice. Interestingly, we found that hIL-7 increased T lymphocyte numbers in the spleens of HIV infected HIS mice without affecting viral load. Taken together, our study unveils a versatile approach to deliver human cytokines to HIS mice, to both improve engraftment and determine the impact of cytokines on human diseases

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care

Impaired perception of facial motion in autism spectrum disorder

Copyright: © 2014 O’Brien 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 credited.This article has been made available through the Brunel Open Access Publishing Fund.Facial motion is a special type of biological motion that transmits cues for socio-emotional communication and enables the discrimination of properties such as gender and identity. We used animated average faces to examine the ability of adults with autism spectrum disorders (ASD) to perceive facial motion. Participants completed increasingly difficult tasks involving the discrimination of (1) sequences of facial motion, (2) the identity of individuals based on their facial motion and (3) the gender of individuals. Stimuli were presented in both upright and upside-down orientations to test for the difference in inversion effects often found when comparing ASD with controls in face perception. The ASD group’s performance was impaired relative to the control group in all three tasks and unlike the control group, the individuals with ASD failed to show an inversion effect. These results point to a deficit in facial biological motion processing in people with autism, which we suggest is linked to deficits in lower level motion processing we have previously reported

Bilateral myositis ossificans of the masseter muscle after chemoradiotherapy and critical illness neuropathy- report of a rare entity and review of literature

Myositis ossificans in the head and neck is a rare heterotropic bone formation within a muscle. Besides fibrodysplasia ossificans progressiva, traumatic and neurogenic forms are described in the literature

The scientific basis of climate-smart agriculture: A systematic review protocol

Background: ‘Climate-smart agriculture’ (CSA)—agriculture and food systems that sustainably increase food production, improve resilience (or adaptive capacity) of farming systems, and mitigate climate change when possible—has quickly been integrated into the global development agenda. However, the empirical evidence base for CSA has not been assembled, complicating the transition from CSA concept to concrete actions, and contributing to ideological disagreement among development practitioners. Thus, there is an urgent need to evaluate current knowledge on the effectiveness of CSA to achieve its intended benefits and inform discourse on food, agriculture, and climate change. This systematic review intends to establish the scientific evidence base of CSA practices to inform the next steps in development of agricultural programming and policy. We will evaluate the impact of 73 promising farm-level management practices across five categories (agronomy, agroforestry, livestock, postharvest management, and energy systems) to assess their contributions to the three CSA pillars: (1) agronomic and economic productivity, (2) resilience and adaptive capacity, and (3) climate change mitigation in the developing world. The resulting data will be compiled into a searchable Web-based database and analytical engine that can be used to assess the relative effectiveness and strength of evidence for CSA, as well as identify best-fit practices for specific farming and development contexts. This represents the largest meta-analysis of agricultural practices to date. Methods/Design: This protocol sets out the approach for investigating the question: How do farm-level CSA management practices and technologies affect food production and/or farmers’ incomes, resilience/adaptive capacity, and climate change mitigation in farming systems of developing countries? The objective of this ongoing systematic review is to provide a first appraisal of the evidence for CSA practices in order to inform subsequent programming. The review is based on data found in English-language peer-reviewed journals with searches using terms relevant to CSA practices and CSA outcomes. Searches were conducted via Web of Science (WoS) and Scopus. Articles located were screened first by abstract and then full text according to predefined eligibility criteria for inclusion in the review. Data capturing the context of the study (e.g., geographic location, environmental context), management practices, and impacts (e.g., indicators of CSA outcomes) will be compiled from those studies that meet the predetermined criteria. Statistical relationships between practices and impacts will be evaluated via meta-analytical approaches including response ratios and effect sizes. Mechanisms to identify bias and maintain consistency continue to be applied throughout the review process. These analyses will be complemented with an analysis of determinants of/barriers to adoption of promising CSA practices covered in the meta-analysis. Results of the review will be incorporated into a publicly available Web-based database. Data will be publicly available under Creative Commons License in 2016

Human Papilloma Virus (HPV) Oral Prevalence in Scotland (HOPSCOTCH):a feasibility study in dental settings

The purpose of this study was to test the feasibility of undertaking a full population investigation into the prevalence, incidence, and persistence of oral Human Papilloma Virus (HPV) in Scotland via dental settings. Male and female patients aged 16-69 years were recruited by Research Nurses in 3 primary care and dental outreach teaching centres and 2 General Dental Practices (GDPs), and by Dental Care Teams in 2 further GDPs. Participants completed a questionnaire (via an online tablet computer or paper) with socioeconomic, lifestyle, and sexual history items; and were followed up at 6-months for further questionnaire through appointment or post/online. Saline oral gargle/rinse samples, collected at baseline and follow-up, were subject to molecular HPV genotyping centrally. 1213 dental patients were approached and 402 individuals consented (participation rate 33.1%). 390 completed the baseline questionnaire and 380 provided a baseline oral specimen. Follow-up rate was 61.6% at 6 months. While recruitment was no different in Research Nurse vs Dental Care Team models the Nurse model ensured more rapid recruitment. There were relatively few missing responses in the questionnaire and high levels of disclosure of risk behaviours (99% answered some of the sexual history questions). Data linkage of participant data to routine health records including HPV vaccination data was successful with 99.1% matching. Oral rinse/gargle sample collection and subsequent HPV testing was feasible. Preliminary analyses found over 95% of samples to be valid for molecular HPV detection prevalence of oral HPV infection of 5.5% (95%CI 3.7, 8.3). It is feasible to recruit and follow-up dental patients largely representative / reflective of the wider population, suggesting it would be possible to undertake a study to investigate the prevalence, incidence, and determinants of oral HPV infection in dental settings

CASZ1b, the Short Isoform of CASZ1 Gene, Coexpresses with CASZ1a during Neurogenesis and Suppresses Neuroblastoma Cell Growth

In Drosophila, the CASZ1 (castor) gene encodes a zinc finger transcription factor and is a neural fate-determination gene. In mammals, the CASZ1 gene encodes two major isoforms, CASZ1a with 11 zinc fingers and CASZ1b with 5 zinc fingers. CASZ1b is more evolutionally conserved since it is the only homologue found in drosophila and Xenopus. Our previous study showed that full length CASZ1 (CASZ1a) functions to suppress growth in neuroblastoma tumor. However, the function of CASZ1b isoform in mammals is unknown. In this study, realtime PCR analyses indicate that mouse CASZ1b (mCASZ1b) is dynamically expressed during neurogenesis. CASZ1b and CASZ1a co-exist in all the neuronal tissues but exhibit distinct expression patterns spatially and temporally during brain development. CASZ1b and CASZ1a expression is coordinately upregulated by the differentiation agent Retinoic Acid, as well as agents that modify the epigenome in neural crest derived neuroblastoma cell lines. In contrast CASZ1b is down regulated while CASZ1a is upregulated by agents that raise intracellular cAMP levels. CASZ1b and CASZ1a have no synergistic or antagonistic activities on the regulation of their target NGFR gene transcription. Specific restoration of CASZ1b in NB cells suppresses tumor growth in vitro and in vivo. Consistent with its function role, we find that low CASZ1b expression is significantly associated with decreased survival probability of neuroblastoma patients (p<0.02). This study indicates that although their mechanisms of regulation may be distinct, both CASZ1b and CASZ1a have largely redundant but critical roles in suppressing tumor cell growth