Mimicking the tumour microenvironment (TME): Angiogenesis in tumour progression

Two-dimensional (2D) substrates cannot accurately mimic the complex matrix of native TME, whereas 3D models can recapitulate the natural tumour progression in vitro. As part of the tumour stroma, fibroblasts and endothelial cells (ECs) are well-known to not only support tumour growth but also to reduce the efficacy of anti-cancer drugs. Particularly, ECs are involved in the process of tumour vascularisation which represents a crucial step in the progression of cancer. Most of the previous studies are carried out in animal models or 2D cultures; hence, a detailed evaluation of experimental data is poor. To address this issue, we aim to develop a novel 3D in vitro approach, to mimic native tumour angiogenesis in 3D and to quantify the developed vascular network.

Telomere length in circulating leukocytes is associated with lung function and disease

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= −0.0452, p=0.024) as well as COPD (β= −0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10−7), FVC (p=2.07×10−5), and FEV1/FVC (p=5.27×10−3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

Instant coffee with high chlorogenic acid levels protects humans against oxidative damage of macromolecules

Scope: Coffee is among the most frequently consumed beverages. Its consumption is inversely associated to the incidence of diseases related to reactive oxygen species; the phenomenon may be due to its antioxidant properties. Our primary objective was to investigate the impact of consumption of a coffee containing high levels of chlorogenic acids on the oxidation of proteins, DNA and membrane lipids; additionally, other redox biomarkers were monitored in an intervention trial. Methods and results: The treatment group (n=36) consumed instant coffee co-extracted from green and roasted beans, whereas the control consumed water (800 mL/P/day, 5 days). A global statistical analysis of four main biomarkers selected as primary outcomes showed that the overall changes are significant. 8-Isoprostaglandin F2α in urine declined by 15.3%, 3-nitrotyrosine was decreased by 16.1%, DNA migration due to oxidized purines and pyrimidines was (not significantly) reduced in lymphocytes by 12.5 and 14.1%. Other markers such as the total antioxidant capacity were moderately increased; e.g. LDL and malondialdehyde were shifted towards a non-significant reduction. Conclusion: The oxidation of DNA, lipids and proteins associated with the incidence of various diseases and the protection against their oxidative damage may be indicative for beneficial health effects of coffee.

Extending the validity of the Feeding Practices and Structure Questionnaire

Background Feeding practices are commonly examined as potentially modifiable determinants of children’s eating behaviours and weight status. Although a variety of questionnaires exist to assess different feeding aspects, many lack thorough reliability and validity testing. The Feeding Practices and Structure Questionnaire (FPSQ) is a tool designed to measure early feeding practices related to non-responsive feeding and structure of the meal environment. Face validity, factorial validity, internal reliability and cross-sectional correlations with children’s eating behaviours have been established in mothers with 2-year-old children. The aim of the present study was to further extend the validity of the FPSQ by examining factorial, construct and predictive validity, and stability. Methods Participants were from the NOURISH randomised controlled trial which evaluated an intervention with first-time mothers designed to promote protective feeding practices. Maternal feeding practices (FP) and child eating behaviours were assessed when children were aged 2 years and 3.7 years (n=388). Confirmatory Factor analysis, group differences, predictive relationships, and stability were tested. Results The original 9-factor structure was confirmed when children were aged 3.7±0.3 years. Cronbach’s alpha was above the recommended 0.70 cut-off for all factors except Structured Meal Timing, Over Restriction and Distrust in Appetite which were 0.58, 0.67 and 0.66 respectively. Allocated group differences reflected behaviour consistent with intervention content and all feeding practices were stable across both time points (range of r= 0.45-0.70). There was some evidence for the predictive validity of factors with 2 FP showing expected relationships, 2 FP showing expected and unexpected relationships and 5 FP showing no relationship. Conclusions Reliability and validity was demonstrated for most subscales of the FPSQ. Future validation is warranted with culturally diverse samples and with fathers and other caregivers. The use of additional outcomes to further explore predictive validity is recommended as well as testing construct validity and test-retest reliability of the questionnaire.

In vitro modeling of the prostate cancer microenvironment

Prostate cancer is the most commonly diagnosed malignancy in men and advanced disease is incurable. Model systems are a fundamental tool for research and many in vitro models of prostate cancer use cancer cell lines in monoculture. Although these have yielded significant insight they are inherently limited by virtue of their two-dimensional (2D) growth and inability to include the influence of tumour microenvironment. These major limitations can be overcome with the development of newer systems that more faithfully recreate and mimic the complex in vivo multi-cellular, three-dimensional (3D) microenvironment. This article presents the current state of in vitro models for prostate cancer, with particular emphasis on 3D systems and the challenges that remain before their potential to advance our understanding of prostate disease and aid in the development and testing of new therapeutic agents can be realised.

In vitro pre-vascularisation of tissue-engineered constructs: A co-culture perspective

In vitro pre-vascularization is one of the main vascularization strategies in the tissue engineering field. Culturing cells within a tissue-engineered construct (TEC) prior to implantation provides researchers with a greater degree of control over the fate of the cells. However, balancing the diverse range of different cell culture parameters in vitro is seldom easy and in most cases, especially in highly vascularized tissues, more than one cell type will reside within the cell culture system. Culturing multiple cell types in the same construct presents its own unique challenges and pitfalls. The following review examines endothelial-driven vascularization and evaluates the direct and indirect role other cell types have in vessel and capillary formation. The article then analyses the different parameters researchers can modulate in a co-culture system in order to design optimal tissue-engineered constructs to match desired clinical applications.

ISPCAN child abuse screening tool children's version (ICAST-C): Instrument development and multi-national pilot testing

Objective To develop a child victimization survey among a diverse group of child protection experts and examine the performance of the instrument through a set of international pilot studies. Methods The initial draft of the instrument was developed after input from scientists and practitioners representing 40 countries. Volunteers from the larger group of scientists participating in the Delphi review of the ICAST P and R reviewed the ICAST C by email in 2 rounds resulting in a final instrument. The ICAST C was then translated and back translated into six languages and field tested in four countries using a convenience sample of 571 children 12–17 years of age selected from schools and classrooms to which the investigators had easy access. Results The final ICAST C Home has 38 items and the ICAST C Institution has 44 items. These items serve as screeners and positive endorsements are followed by queries for frequency and perpetrator. Half of respondents were boys (49%). Endorsement for various forms of victimization ranged from 0 to 51%. Many children report violence exposure (51%), physical victimization (55%), psychological victimization (66%), sexual victimization (18%), and neglect in their homes (37%) in the last year. High rates of physical victimization (57%), psychological victimization (59%), and sexual victimization (22%) were also reported in schools in the last year. Internal consistency was moderate to high (alpha between .685 and .855) and missing data low (less than 1.5% for all but one item). Conclusions In pilot testing, the ICAST C identifies high rates of child victimization in all domains. Rates of missing data are low, and internal consistency is moderate to high. Pilot testing demonstrated the feasibility of using child self-report as one strategy to assess child victimization. Practice implications The ICAST C is a multi-national, multi-lingual, consensus-based survey instrument. It is available in six languages for international research to estimate child victimization. Assessing the prevalence of child victimization is critical in understanding the scope of the problem, setting national and local priorities, and garnering support for program and policy development aimed at child protection.

Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance

In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models.

Using genome-Wwide complex trait analysis to quantify 'missing heritability' in Parkinson's disease

Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI 17-38, P = 8.08E - 08) phenotypic variance associated with all types of PD, 15% (95% CI -0.2 to 33, P = 0.09) phenotypic variance associated with early-onset PD and 31% (95% CI 17-44, P = 1.34E - 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5%) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered. © Published by Oxford University Press 2012.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Breastfeeding duration and authoritative feeding practices in first-time mothers

Background Longer breastfeeding duration appears to have a protective effect against childhood obesity. This effect may be partially mediated by maternal feeding practices during the first years of life. However, the few studies that have examined links between breastfeeding duration and subsequent feeding practices have yielded conflicting results. Objective Using a large sample of first-time mothers and a newly validated, comprehensive measure of maternal feeding (the Feeding Practices and Structure Questionnaire1), this study examined associations between breastfeeding duration and maternal feeding practices at child age 24 months. Methods Mothers (n = 458) enrolled in the NOURISH trial2 provided data on breastfeeding at child age 4, 14 and 24 months, and on feeding practices at 24 months. Structural Equation Modelling was used to examine associations between breastfeeding duration and five non-responsive and four structure-related ‘authoritative’ feeding practices, adjusting for a range of maternal and child characteristics. Results The model showed acceptable fit (χ2/df = 1.68; RMSEA = .04, CFI = .91 and TLI = .89) and longer breastfeeding duration was negatively associated with four out of five non-responsive feeding practices and positively associated with three out of four structure-related feeding practices. Overall, these results suggest that mothers who breastfeed longer reported using more appropriate feeding practices. Conclusion These data demonstrate an association between longer breastfeeding duration and authoritative feeding practices characterised by responsiveness and structure, which may partly account for the apparent protective effect of breastfeeding on childhood obesity.

"Minäkin olen täällä löyhkäämässä" : Etnisyyden ja ruumiillisuuden representaatiot Veronica Pimenoffin romaanissa Maa ilman vettä

Tutkin työssäni, miten etnisyys ja ruumiillisuus representoituvat Veronica Pimenoffin romaanissa Maa ilman vettä (1999) ja millaisia merkityksiä nämä representaatiot saavat suhteessa kysymyksiin vallasta, väkivallasta, sukupuolesta, seksuaalisuudesta, hyvinvoinnista ja sairaudesta. Tutkimukseni teoreettisena viitekehyksenä on jälkikoloniaalinen teoria. Romaanissa on keskeisellä tavalla kyse konfliktista: nuoruudenystävykset, suomalainen Kristiina ja mosambikilainen Sofia Elena, kohtaavat jälkimmäisen kuolinvuoteella ja käyvät kiivasta kamppailua aatteista ja arvoista. Olen tulkinnut romaanin päähenkilöt allegorisiksi hahmoiksi, jotka edustavat kotimaitaan ja -mantereitaan. Näihin henkilöhahmoihin kiteytyy ominaisuuksia, jotka tavataan hahmottaa stereotyyppisiksi Euroopalle ja Afrikalle. Etnisyys representoituu paitsi Kristiinan ja Sofia Elenan tyypitellyissä luonteenpiirteissä ja käyttäytymismalleissa myös heidän ulkonäkönsä kuvauksessa. Kristiina kuvataan korostetun vaaleana ja Sofia Elena korostetun mustana, minkä voi tulkita kommentoivan imperialistiseen diskurssiin liittyvää binaarista ajattelua. Myös romaanin miehet ovat tulkittavissa allegorisiksi hahmoiksi: Kristiinan mies Otto edustaa vaimonsa tavoin vaurasta Eurooppaa, amerikkalainen pohatta Mark Hunter Yhdysvaltoja ja sen mahtia ja Kristiinan nuoruudenrakastettu Abdel läntistä kuvitelmaa eksoottisesta Orientista. Ruumiillisuus korostuu romaanissa seksuaalisuuden, sairauden ja väkivallan kuvauksissa. Kristiina on seksuaalinen toteuttaja, jonka kokemus omasta ruumiista määräytyy pitkältä eroottisten kokemusten perusteella. Sofia Elenaa taas ei kuvata seksuaalisena hahmona, vaan hänen kehonsa kuvausta hallitsee sairaus. Koska Sofia Elena on allegorinen hahmo, hänen ruumiinsa voi rinnastaa mantereeseen ja sitä riuduttava sairaus prosesseihin, jotka tunkeutuvat yhteiskuntien rakenteisiin ja nakertavat niitä sisältäpäin: hallitsemattomaan kansainväliseen muuttoliikkeeseen, rikollisuuteen ja terrorismiin. Sofia Elenalla on kokemusta myös väkivallasta: hän on sotinut ja pitää väkivaltaa ainoana keinona taistella Länttä vastaan. Romaani välittää kuitenkin pessimistisen kuvan väkivallan mahdollisuudesta vapauttaa (kolmannen maailman) naiset. Pessimistinen kuva välittyy myös ensimmäisen ja kolmannen maailman naisten mahdollisuuksista ymmärtää toisiaan. Nais-Afrikka ja nais-Eurooppa jäävät romaanissa etäälle toisistaan sekä henkisesti että fyysisesti.

Classical Biological Control for the Protection of Natural Ecosystems.

Of the 70 cases of classical biological control for the protection of nature found in our review, there were fewer projects against insect targets (21) than against invasive plants (49), in part, because many insect biological control projects were carried out against agricultural pests, while nearly all projects against plants targeted invasive plants in natural ecosystems. Of 21 insect projects, 81% (17) provided benefits to protection of biodiversity, while 48% (10) protected products harvested from natural systems, and 5% (1) preserved ecosystem services, with many projects contributing to more than one goal. In contrast, of the 49 projects against invasive plants, 98% (48) provided benefits to protection of biodiversity, while 47% (23) protected products, and 25% (12) preserved ecosystem services, again with many projects contributing to several goals. We classified projects into complete control (pest generally no longer important), partial control (control in some areas but not others), and "in progress," for projects in development for which outcomes do not yet exist. For insects, of the 21 projects discussed, 59% (13) achieved complete control of the target pest, 18% (4) provided partial control, and 41% (9) are still in progress. By comparison, of the 49 invasive plant projects considered, 27% (13) achieved complete control, while 33% (16) provided partial control, and 47% (24) are still in progress. For both categories of pests, some projects' success ratings were scored twice when results varied by region. We found approximately twice as many projects directed against invasive plants than insects and that protection of biodiversity was the most frequent benefit of both insect and plant projects. Ecosystem service protection was provided in the fewest cases by either insect or plant biological control agents, but was more likely to be provided by projects directed against invasive plants, likely because of the strong effects plants exert on landscapes. Rates of complete success appeared to be higher for insect than plant targets (59% vs 27%), perhaps because most often herbivores gradually weaken, rather than outright kill, their hosts, which is not the case for natural enemies directed against pest insects. For both insect and plant biological control, nearly half of all projects reviewed were listed as currently in progress, suggesting that the use of biological control for the protection of wildlands is currently very active.