Cerebral Malaria in Mouse and Man

Cerebral malaria (CM) is an acute encephalopathy caused by the malaria parasite Plasmodium falciparum, which develops in a small minority of infected patients and is responsible for the majority of deaths in African children. Despite decades of research on CM, the pathogenic mechanisms are still relatively poorly defined. Nevertheless, many studies in recent years, using a combination of animal models, in vitro cell culture work, and human patients, provide significant insight into the pathologic mechanisms leading to CM. In this review, we summarize recent findings from mouse models and human studies on the pathogenesis of CM, understanding of which may enable development of novel therapeutic approaches

Targeting Leader Cells in Ovarian Cancer as an Effective Therapeutic Option

Majority of ovarian cancers are diagnosed at advanced stages with intra-peritoneal spread as the most common mode of disease metastasis. The formation of cancer spheroids is essential for the collective migration process, where shed tumour cells from the primary tumour form aggregates rather than disseminating as individual cells and seed within the peritoneal cavity. These cancer spheroids consist of leader cells (LC) and follower cells (FC), with the LC subset as key drivers of cellular movement and invasion. LCs have stem cell-like properties and are highly chemo-resistant with a specific survival addiction to several cell signalling pathways, such as the PI3K/AKT/mTOR pathway. We explore in this book chapter, the evidence supporting the role of LC in OC metastasis and the suppression of LC as an attractive therapeutic option for the treatment of advanced OC

Maximizing information : a machine learning approach for analysis of complex nanoscale electromechanical behavior in defect-rich PZT films

F.Z. and B.J.R. gratefully acknowledge support from the China Scholarship Council and Science Foundation Ireland (US-Ireland R&D Partnership Programme (SFI/14/US/I3113) and Career Development Award (SFI/17/CDA/4637) with support from the Sustainable Energy Authority of Ireland). A.N. gratefully acknowledges support from the Engineering and Physics Sciences Research Council (EPSRC) through grants EP/R023751/1 and EP/L017008/1. A.K. gratefully acknowledges support from Department of Education and Learning NI through grant USI-082 and Engineering and Physical Sciences Research Council via grant EP/S037179/1. K.W., Y.Y., and N.B.G. gratefully acknowledge support from the US National Science Foundation through grant CMMI-1537262 and DMR-1255379. K.W. and N.B.G. also acknowledge support through DMR-2026976. This publication has emanated from research supported in part by a grant from Science Foundation Ireland under Grant numbers SFI/14/US/I3113 and SFI/17/CDA/4637.Scanning Probe Microscopy (SPM) based techniques probe material properties over microscale regions with nanoscale resolution, ultimately resulting in investigation of mesoscale functionalities. Among SPM techniques, piezoresponse force microscopy (PFM) is a highly effective tool in exploring polarization switching in ferroelectric materials. However, its signal is also sensitive to sample-dependent electrostatic and chemo-electromechanical changes. Literature reports have often concentrated on the evaluation of the Off-field piezoresponse, compared to On-field piezoresponse, based on the latter's increased sensitivity to non-ferroelectric contributions. Using machine learning approaches incorporating both Off- and On-field piezoresponse response as well as Off-field resonance frequency to maximize information, switching piezoresponse in a defect-rich Pb(Zr,Ti)O3 thin film is investigated. As expected, one major contributor to the piezoresponse is mostly ferroelectric, coupled with electrostatic phenomena during On-field measurements. A second component is electrostatic in nature, while a third component is likely due to a superposition of multiple non-ferroelectric processes. The proposed approach will enable deeper understanding of switching phenomena in weakly ferroelectric samples and materials with large chemo-electromechanical response.Publisher PDFPeer reviewe

Attitudes of parents towards the ‘Fit Together’ childhood obesity prevention programme: a qualitative study

Background: The latest available data for England show that childhood obesity continues to be a major public health concern with 9.3% of 4–5 years old and 18.9% of 10–11 years old children found to be obese (1). The aim of the study was to explore attitudes towards a community based childhood obesity prevention project among parents participating in the programme. Methods: The ‘Fit Together’ programme was provided in socio-economically deprived areas of Leeds which, at the time of the research study, was in its final year of running. The programme was delivered for 2 hours each week over a six week period by community health educators, and involved health education and cooking sessions. A convenience sample of parents who had attended at least one session of the Fit Together programme, delivered between November-December 2014, were recruited from a children’s centre (where families access health advice and related activities with their children aged 0– 5yr) and a primary school. Semi-structured interviews were conducted using a topic schedule with prompts, and were digitally recorded. A short screening questionnaire was completed to obtain demographic information. Three parents were present in each of the two Fit Together sessions allocated for recruitment. These six parents were recruited to the study and were interviewed. Interviews were transcribed verbatim, transcripts manually coded and thematic analysis conducted using a framework approach. Ethical approval for the study was obtained from the Faculty of Health & Social Sciences Local Research Ethics Coordinator, Leeds Beckett University. Results: Participants were all mothers with 1–3 children, and mean age was 27 years. Four participants self-defined their ethnicity as White British and the remaining two as Pakistani. Themes emerging from the interview data suggested that participants’ appraisal of the programme was positive and they reported benefits in behaviour change relevant to addressing childhood obesity. Parents felt the programme was logistically suitable, and had appropriate content and leaders. All participants would recommend the programme and highlighted the development of their cooking skills, which related to an increase in home cooking and in fruit and vegetable consumption. The opportunity to involve their children and spend time with them learning skills was a strongly held view among respondents. Parents felt the programme had also increased their awareness of nutrition content and children’s dietary habits. However, the view that an extended programme and subsequent follow-up were needed was commonly held. Additional benefits beyond behaviour change were also expressed. For example, the importance of social interaction was clear, with respondents reporting the alleviation of boredom and isolation while attending the programme, as this participant states: “Something to do ain’t it? Gets you out. There’s nothing else to go to” (White British, 23yr, 2 children). Participants also reported exchanging cultural beliefs and learning new styles of cooking from people from different backgrounds. Discussion: The findings of this first exploration of parents’ attitudes to Fit Together supports existing literature on the value of community educators in delivering health interventions (2). Beneficial behaviour change such as increased homecooking was consistent with previous programmes (3). Conclusion: Attitudes towards Fit Together were positive, with mothers viewing the programme as acceptable and bene- ficial. References 1. Stevens. L., & Nelson, M. The contribution of school meals and packed lunch to food consumption and nutrient intakes in UK primary school children from a low income population. Journal of Human Nutrition and Dietetics, 24; 223–232. 2011. 2. Evans, C., & Harper, C. A History and Review of school meals standards in the UK. Journal of Human Nutrition and Dietetics, 89–99. 2009. 3. Lop ez Nomdedeu, C. Agencia Espanola de Seguridad Alimentaria y Nutricion. Ministerio de Sanidad y Consum. La alimentacion de tus ni nos. Nutrici ~ on Saludable de la Infan- cia a la Adolescencia. Madrid: Fiselgraf, S.L. 2002

Self-rated health in middle-aged and elderly Chinese : distribution, determinants and associations with cardio-metabolic risk factors

Background: Self-rated health (SRH) has been demonstrated to be an accurate reflection of a person's health and a valid predictor of incident mortality and chronic morbidity. We aimed to evaluate the distribution and factors associated with SRH and its association with biomarkers of cardio-metabolic diseases among middle-aged and elderly Chinese. Methods: Survey of 1,458 men and 1,831 women aged 50 to 70 years, conducted in one urban and two rural areas of Beijing and Shanghai in 2005. SRH status was measured and categorized as good (very good and good) vs. not good (fair, poor and very poor). Determinants of SRH and associations with biomarkers of cardio-metabolic diseases were evaluated using logistic regression. Results: Thirty two percent of participants reported good SRH. Males and rural residents tended to report good SRH. After adjusting for potential confounders, residence, physical activity, employment status, sleep quality and presence of diabetes, cardiovascular disease, and depression were the main determinants of SRH. Those free from cardiovascular disease (OR 3.68; 95%CI 2.39; 5.66), rural residents (OR 1.89; 95% CI 1.47; 2.43), non-depressed participants (OR 2.50; 95% CI 1.67; 3.73) and those with good sleep quality (OR 2.95; 95% CI 2.22; 3.91) had almost twice or over the chance of reporting good SRH compared to their counterparts. There were significant associations -and trend- between SRH and levels of inflammatory markers, insulin levels and insulin resistance. Conclusion: Only one third of middle-aged and elderly Chinese assessed their health status as good or very good. Although further longitudinal studies are required to confirm our findings, interventions targeting social inequalities, lifestyle patterns might not only contribute to prevent chronic morbidity but as well to improve populations' perceived health

Sleep quality in middle-aged and elderly Chinese: distribution, associated factors and associations with cardio-metabolic risk factors

Background Poor sleep quality has been associated with increased risk of heart disease, diabetes and mortality. However, limited information exists on the distribution and determinants of sleep quality and its associations with cardio-metabolic risk factors in Chinese populations. We aimed to evaluate this in the current study. Methods A cross-sectional survey conducted in 2005 of 1,458 men and 1,831 women aged 50–70 years from urban and rural areas of Beijing and Shanghai. Using a questionnaire, sleep quality was measured in levels of well, common and poor. Comprehensive measures of socio-demographical and health factors and biomarkers of cardio-metabolic disease were recorded. These were evaluated in association with sleep quality using logistic regression models. Results Half of the population reported good sleep quality. After adjusting for potential confounders, women and Beijing residents had almost half the probability to report good sleep quality. Good physical and mental health (good levels of self-rated health (OR 2.48; 95%CI 2.08 to 2.96) and no depression (OR 4.05; 95%CI 3.12 to 5.26)) related to an increased chance of reporting good sleep quality, whereas short sleep duration (<7 hrs OR 0.10; 95%CI 0.07 to 0.14)) decreased it substantially. There were significant associations between levels of sleep quality and concentrations of plasma insulin, total and LDL cholesterol, and index of insulin resistance. Conclusion Levels of good sleep quality in middle-age and elderly Chinese were low. Gender, geographical location, self-rated health, depression and sleep quantity were major factors associated with sleep quality. Prospective studies are required to distil the factors that determine sleep quality and the effects that sleep patterns exert on cardio-metabolic health

A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram.

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors. Methods: A retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical analysis. Factors associated with survival time were identified using proportional odds ordinal regression. We constructed a survival-predictive nomogram using a forward stepwise model that we subsequently validated using The Cancer Genome Atlas. Results: Univariate analysis revealed 3 pivotal genetic alterations associated with GBM survival: both high tumor mutational burden ( Conclusions: Our newly devised long-term surviva

Radiographic knee osteoarthritis in ex-elite table tennis players

<p>Abstract</p> <p>Background</p> <p>Table tennis involves adoption of the semi-flexed knee and asymmetrical torsional trunk movements creating rotational torques on the knee joint which may predispose players to osteoarthritis (OA) of the knee. This study aims to compare radiographic signs of knee OA and associated functional levels in ex-elite male table tennis players and control subjects.</p> <p>Methods</p> <p>Study participants were 22 ex-elite male table tennis players (mean age 56.64 ± 5.17 years) with 10 years of involvement at the professional level and 22 non-athletic males (mean age 55.63 ± 4.08 years) recruited from the general population. A set of three radiographs taken from each knee were evaluated by an experienced radiologist using the Kellgren and Lawrence (KL) scale (0-4) to determine radiographic levels of OA severity. The intercondylar distance was taken as a measure of lower limb angulation. Participants also completed the pain, stiffness, and physical function categories of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) 3.1 questionnaire.</p> <p>Results</p> <p>The results showed 78.3% of the ex-elite table tennis players and 36.3% of controls had varying signs of radiographic knee OA with a significant difference in the prevalence levels of definite radiographic OA (KL scale > 2) found between the two groups (<it>P </it>≤ 0.001). Based on the WOMAC scores, 68.2% of the ex-elite table tennis players reported symptoms of knee pain compared with 27.3% of the controls (<it>p </it>= 0.02) though no significant differences were identified in the mean physical function or stiffness scores between the two groups. In terms of knee alignment, 73.7% of the ex-elite athletes and 32% of the control group had signs of altered lower limb alignment (genu varum) (<it>p </it>= 0.01). Statistical differences were found in subjects categorized as having radiographic signs of OA and altered lower limb alignment (<it>p </it>= 0.03).</p> <p>Conclusions</p> <p>Ex-elite table tennis players were found to have increased levels of radiological signs of OA in the knee joint though this did not transpire through to altered levels of physical disability or knee stiffness in these players when compared with subjects from the general population suggesting that function in these players is not severely impacted upon.</p