Combinatorial biomaterials discovery strategy to identify new macromolecular cryoprotectants

Cryoprotective agents (CPAs) are typically solvents or small molecules, but there is a need for innovative CPAs to reduce toxicity and increase cell yield, for the banking and transport of cells. Here we use a photochemical high-throughput discovery platform to identify macromolecular cryoprotectants, as rational design approaches are currently limited by the lack of structure–property relationships. Using liquid handling systems, 120 unique polyampholytes were synthesized using photopolymerization with RAFT agents. Cryopreservation screening identified “hit” polymers and nonlinear trends between composition and function, highlighting the requirement for screening, with polymer aggregation being a key factor. The most active polymers reduced the volume of dimethyl sulfoxide (DMSO) required to cryopreserve a nucleated cell line, demonstrating the potential of this approach to identify materials for cell storage and transport

The stability of food intake between adolescence and adulthood: a 21-year follow-up

Studies of the diet of adolescents in the UK demonstrate that dietary habits known to be detrimental to health in adulthood are evident at an early age. For example, Gregory et al (2000) found 4-18 year olds in the UK to have a frequent consumption of fatty and sugary foods and low consumption of fruit and vegetables. Concerns have therefore been expressed regarding the diet of children and adolescents and the continuation of these dietary habits into adulthood (HEA, 1995; Gaziano, 1998). This study aimed to investigate the extent to which these concerns may be justified by determining the stability of food intake of a group of adolescents followed up 21 years later in adulthood. The investigation involved 202 individuals from whom dietary data were collected in 1979-80 (mean age 11.6 years) (Hackett et al. 1984) and again in 2000-1 (mean age 32.5 years). Dietary data were collected at both time-points using two 3 d estimated food diaries followed by an interview to determine portion sizes using the method considered most appropriate at the time, i.e. calibrated food models in 1979-80 and a photographic food atlas (Nelson et al. 1997) in 2000-1. Foods consumed were allocated to one, or a combination of, the five food groups of the ‘Balance of Good Health’ food selection guide (HEA, 1994) according to Gatenby et al. (1995). The weight of food eaten from each of the five food groups was calculated (percentage of total weight of food consumed) and Pearson correlation coefficients generated to provide an estimate of the stability of food intake. The HEA guide advises that a balanced diet should consist of around 33% fruit and vegetables, 33% bread, other cereals and potatoes, 8% foods containing fat and/or sugar, 12% meat, fish and alternatives and 15% milk and dairy products (Gatenby et al. 1995). A shift in the group’s food intake towards the recommendations had occurred with age, most notably with a decrease in foods containing fat and/or sugar and an increase in fruit and vegetables. Nevertheless, at both ages, intakes of foods containing fat and/or sugar, meat, fish and alternatives were higher, and fruit, vegetables, bread, other cereals and potatoes lower than currently recommended. In addition, although there was significant evidence of tracking of relative intake of bread, cereals and potatoes (P<0.01), fruit and vegetables (P<0.01), and meat, fish and alternatives (P=0.02) between 11.6 and 32.5 years, the correlations were not strong. In conclusion, food intake patterns had changed considerably from early adolescence through to adulthood in a direction more in line with the current recommendations. The predictive value of an adolescent’s food intake of their intake in adulthood was found to be significant, but not strong. Further investigations will consider the extent to which this is influenced by factors such as social class, gender and educational level, as well as assessing tracking in terms of relative nutrient intakes

Projections of Global Mortality and Burden of Disease from 2002 to 2030

BACKGROUND: Global and regional projections of mortality and burden of disease by cause for the years 2000, 2010, and 2030 were published by Murray and Lopez in 1996 as part of the Global Burden of Disease project. These projections, which are based on 1990 data, continue to be widely quoted, although they are substantially outdated; in particular, they substantially underestimated the spread of HIV/AIDS. To address the widespread demand for information on likely future trends in global health, and thereby to support international health policy and priority setting, we have prepared new projections of mortality and burden of disease to 2030 starting from World Health Organization estimates of mortality and burden of disease for 2002. This paper describes the methods, assumptions, input data, and results. METHODS AND FINDINGS: Relatively simple models were used to project future health trends under three scenarios—baseline, optimistic, and pessimistic—based largely on projections of economic and social development, and using the historically observed relationships of these with cause-specific mortality rates. Data inputs have been updated to take account of the greater availability of death registration data and the latest available projections for HIV/AIDS, income, human capital, tobacco smoking, body mass index, and other inputs. In all three scenarios there is a dramatic shift in the distribution of deaths from younger to older ages and from communicable, maternal, perinatal, and nutritional causes to noncommunicable disease causes. The risk of death for children younger than 5 y is projected to fall by nearly 50% in the baseline scenario between 2002 and 2030. The proportion of deaths due to noncommunicable disease is projected to rise from 59% in 2002 to 69% in 2030. Global HIV/AIDS deaths are projected to rise from 2.8 million in 2002 to 6.5 million in 2030 under the baseline scenario, which assumes coverage with antiretroviral drugs reaches 80% by 2012. Under the optimistic scenario, which also assumes increased prevention activity, HIV/AIDS deaths are projected to drop to 3.7 million in 2030. Total tobacco-attributable deaths are projected to rise from 5.4 million in 2005 to 6.4 million in 2015 and 8.3 million in 2030 under our baseline scenario. Tobacco is projected to kill 50% more people in 2015 than HIV/AIDS, and to be responsible for 10% of all deaths globally. The three leading causes of burden of disease in 2030 are projected to include HIV/AIDS, unipolar depressive disorders, and ischaemic heart disease in the baseline and pessimistic scenarios. Road traffic accidents are the fourth leading cause in the baseline scenario, and the third leading cause ahead of ischaemic heart disease in the optimistic scenario. Under the baseline scenario, HIV/AIDS becomes the leading cause of burden of disease in middle- and low-income countries by 2015. CONCLUSIONS: These projections represent a set of three visions of the future for population health, based on certain explicit assumptions. Despite the wide uncertainty ranges around future projections, they enable us to appreciate better the implications for health and health policy of currently observed trends, and the likely impact of fairly certain future trends, such as the ageing of the population, the continued spread of HIV/AIDS in many regions, and the continuation of the epidemiological transition in developing countries. The results depend strongly on the assumption that future mortality trends in poor countries will have a relationship to economic and social development similar to those that have occurred in the higher-income countries

Global and regional estimates of cancer mortality and incidence by site: I. Application of regional cancer survival model to estimate cancer mortality distribution by site

BACKGROUND: The Global Burden of Disease 2000 (GBD 2000) study starts from an analysis of the overall mortality envelope in order to ensure that the cause-specific estimates add to the total all cause mortality by age and sex. For regions where information on the distribution of cancer deaths is not available, a site-specific survival model was developed to estimate the distribution of cancer deaths by site. METHODS: An age-period-cohort model of cancer survival was developed based on data from the Surveillance, Epidemiology, and End Results (SEER). The model was further adjusted for the level of economic development in each region. Combined with the available incidence data, cancer death distributions were estimated and the model estimates were validated against vital registration data from regions other than the United States. RESULTS: Comparison with cancer mortality distribution from vital registration confirmed the validity of this approach. The model also yielded the cancer mortality distribution which is consistent with the estimates based on regional cancer registries. There was a significant variation in relative interval survival across regions, in particular for cancers of bladder, breast, melanoma of the skin, prostate and haematological malignancies. Moderate variations were observed among cancers of colon, rectum, and uterus. Cancers with very poor prognosis such as liver, lung, and pancreas cancers showed very small variations across the regions. CONCLUSIONS: The survival model presented here offers a new approach to the calculation of the distribution of deaths for areas where mortality data are either scarce or unavailable

Measuring Infertility in Populations: Constructing a Standard Definition for Use with Demographic and Reproductive Health Surveys

Background: Infertility is a significant disability, yet there are no reliable estimates of its global prevalence. Studies on infertility prevalence define the condition inconsistently, rendering the comparison of studies or quantitative summaries of the literature difficult. This study analyzed key components of infertility to develop a definition that can be consistently applied to globally available household survey data. Methods: We proposed a standard definition of infertility and used it to generate prevalence estimates using 53 Demographic and Health Surveys (DHS). The analysis was restricted to the subset of DHS that contained detailed fertility information collected through the reproductive health calendar. We performed sensitivity analyses for key components of the definition and used these to inform our recommendations for each element of the definition

Influence of maternal folate depletion on Art3 DNA methylation in the murine adult brain; potential consequences for brain and neurocognitive health

\ua9 The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. The developmental origins of health and disease hypothesis suggest early-life environment impacts health outcomes throughout the life course. In particular, epigenetic marks, including DNA methylation, are thought to be key mechanisms through which environmental exposures pro-gramme later-life health. Adequate maternal folate status before and during pregnancy is essential in the protection against neural tube defects, but data are emerging that suggest early-life folate exposures may also influence neurocognitive outcomes in childhood and, potentially, thereafter. Since folate is key to the supply of methyl donors for DNA methylation, we hypothesize that DNA methylation may be a mediating mechanism through which maternal folate influences neurocognitive outcomes. Using bisulphite sequencing, we measured DNA methylation of five genes (Art3, Rsp16, Tspo, Wnt16, and Pcdhb6) in the brain tissue of adult offspring of dams who were depleted of folate (n = 5, 0.4 mg folic acid/kg diet) during pregnancy (~19-21 days) and lactation (mean 22 days) compared with controls (n = 6, 2 mg folic acid/kg diet). Genes were selected as methylation of their promoters had previously been found to be altered by maternal folate intake in mice and humans across the life course, and because they have potential associations with neurocognitive outcomes. Maternal folate depletion was significantly associated with Art3 gene hypomethylation in subcortical brain tissue of adult mice at 28 weeks of age (mean decrease 6.2%, P = .03). For the other genes, no statistically significant differences were found between folate depleted and control groups. Given its association with neurocognitive outcomes, we suggest Art3 warrants further study in the context of lifecourse brain health. We have uncovered a potential biomarker that, once validated in accessible biospecimens and human context, may be useful to track the impact of early-life folate exposure on later-life neurocognitive health, and potentially be used to develop and monitor the effects of interventions