A processive versus a distributive mechanism of action correlates with differences in ability of normal and xeroderma pigmentosum group A endonucleases to incise damaged nucleosomal DNA

A DNA endonuclease, isolated from the nuclei of normal human and xeroderma pigmentosum complementation group A (XPA) cells, which recognizes predominately pyrimidine dimers, was examined for the mechanism by which it locates sites of damage on UVC-irradiated DNA. In reaction mixtures with low ionic strengths (i.e. lacking KCl), the normal and XPA endonuclease locate sites of UV damage on both naked and reconstituted nucleosomal DNA by different mechanisms. On both of these substrates, the normal endonuclease acts by a processive mechanism, meaning that it binds non-specifically to DNA and scans the DNA for sites of damage, whereas the XPA endonuclease acts by a distributive one, meaning that it randomly locates sites of damage on DNA. However, while both the normal and XPA endonucleases can incise UVC irradiated naked DNA, they differ in ability to incise damaged nucleosomal DNA. The normal endonuclease showed increased activity on UVC treated nucleosomal DNA compared with naked DNA, whereas the XPA endonuclease showed decreased activity on the damaged nucleosomal substrate. Since a processive mechanism of action is sensitive to the ionic strength of the micro-environment, the KCl concentration of the reaction was increased. At 70 mM KCI, the normal endonuclease switched to a distributive mechanism of action and its ability to incise damaged nucleosomal DNA also decreased. These studies show that there is a correlation between the ability of these endonucleases to act by a processive mechanism and their ability to incise damaged nucleosomal DNA; the normal endonuclease, which acts processively, can incise damaged nucleosomal DNA, whereas the XPA endonuclease, which acts distributively, is defective in ability to incise this substrate.      

A new amino acid mixture permits new approaches to the treatment of phenylketonuria

A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance.     

Population health. More than the sum of the parts?

The past decade has seen an upsurge of interest in the development of summary measures of population health. Almost invariably the measures have relied on "rolling up" individual level health data such as mortality data or life expectancy data. The approach, however, of treating population health as a synthesis of aggregated individual level data is a historical and statistical convenience. Although there has been some debate in the literature about whether one should also examine the equity of the distribution of health, the general practice has been to treat the level of a population's health and the distribution of health within a population as separate issues. Without recourse to contentious notions of equity, this paper examines the possibility of treating populations as more than simply the sum of their parts by combining individual level health data with population level data about the distribution of health. This approach may provide policy makers with additional ways of thinking about what it means to improve a population's health.     

Future research on structural and institutional forms of HIV discrimination

There is scant research into HIV discrimination, particularly structural and institutional forms of it. This appears, in part, to arise from a prevailing view that the solutions to HIV discrimination are known a priori and in the absence of additional data. The six country studies into HIV discrimination presented in this AIDS Care supplement suggest that this is not the case. There needs to be an acceptance that if the issue of HIV discrimination is to be tackled successfully and based on evidence, then incremental and effortful steps need to be taken to develop that evidence base. This is discussed.     

Handgrip strength in English schoolchildren

Aims: The aims of this study were to evaluate patterns of handgrip (HG) strength in relation to gender and age in English schoolchildren and to compare this with existing data and produce reference data for this population. Methods: The HG of 7147 English schoolchildren (3773 boys and 3374 girls) aged 10–15.9 years was measured using a portable Takei handgrip dynamometer (Takei Scientific Instruments Co. Ltd, Tokyo, Japan). Centile data were produced using the Generalized Additive Models for Location, Scale and Shape. Z‐scores were generated using existing data for European children. Age and gender interactions were analysed using analysis of covariance. Results: In boys and girls, significant increases in HG were found between every age‐group (p < 0.001). Boys were significantly stronger than girls at every age (p < 0.001) and the boys’ age‐related increase was significantly greater than the girls’ (p < 0.001). Conclusion: This study provides reference data for handgrip strength in English schoolchildren. Handgrip strength in English children is broadly similar to existing European data, after adjusting for mass and stature. These data could be used for clinical or athletic screening of low and high strength in this population.     

China's rural-urban care gap shrank for chronic disease patients, but inequities persist

Reducing the gap in health outcomes between rural and urban areas in China has been a focus of the central government's health reform efforts since 2002. Drawing on national survey data from 2003 and 2008, this paper analyzes changes in the rural-urban gap for patients with chronic diseases. Overall, there were substantial improvements at the national level in insurance coverage and the use of hospital services for both urban and rural residents with chronic diseases. There was also an overall reduction in the rural-urban gap in the use of inpatient services. But the gains were uneven. For example, although rural Chinese with chronic disease could more easily start inpatient treatment in 2008 than they could in 2003, because of the higher hospital copayments required under insurance coverage for rural citizens, they were more than twice as likely to drop out of treatment as were Chinese in urban areas. The strongest evidence of the narrowing of the rural-urban gap came from central China, while the evidence is mixed for western and eastern China. Our analysis suggests that different approaches will be required to narrow the rural-urban health service gap in different regions of China.     

An overview of health forecasting

Health forecasting is a novel area of forecasting, and a valuable tool for predicting future health events or situations such as demands for health services and healthcare needs. It facilitates preventive medicine and health care intervention strategies, by pre-informing health service providers to take appropriate mitigating actions to minimize risks and manage demand. Health forecasting requires reliable data, information and appropriate analytical tools for the prediction of specific health conditions or situations. There is no single approach to health forecasting, and so various methods have often been adopted to forecast aggregate or specific health conditions. Meanwhile, there are no defined health forecasting horizons (time frames) to match the choices of health forecasting methods/approaches that are often applied. The key principles of health forecasting have not also been adequately described to guide the process. This paper provides a brief introduction and theoretical analysis of health forecasting. It describes the key issues that are important for health forecasting, including: definitions, principles of health forecasting, and the properties of health data, which influence the choices of health forecasting methods. Other matters related to the value of health forecasting, and the general challenges associated with developing and using health forecasting services are discussed. This overview is a stimulus for further discussions on standardizing health forecasting approaches and methods that will facilitate health care and health services delivery.