Lactoferrin and cancer in different cancer models

Lactoferrin (Lf) is a multifunctional protein and an essential element of innate immunity. Cancer is a major killer in today's world accounting for around 13% of all deaths according to the World Health Organisation (W.H.O.). The five most common forms of cancer include lung, colorectal, stomach, liver and breast cancer. Lactoferrin is a natural forming iron-binding glycoprotein with antibacterial, antioxidant and anti-carcinogenic effects. It is produced in exocrine glands and is secreted in many external fluids as a first line of defence. Lactoferrin also has the capacity to induce apoptosis and inhibit proliferation in cancer cells as well as restore white and red blood cell levels after chemotherapy. This review focuses on the therapeutic effect bovine sourced lactoferrin has on various forms of cancer in various models. It also focuses on the benefits of 3D in vitro cell culture. 3D cell culture has vast advantages over 2D models including demonstration of realistic therapeutic results and heightened resistance that 2D models fail to display.

Applications of nanomedicine in antibacterial medical therapeutics and diagnostics

The need for new and effective/efficient antibacterial therapeutics and diagnostics is necessary if we want to be able to maintain and improve the protection against pathogenic bacteria. Bacteria are becoming increasingly resistant to traditionally used antibiotics and as a result are a major health concern. The number of deaths and hospitalizations due to bacteria is increasing. Current methods of bacterial diagnostics are inefficient as they lack speed and ultra sensitivity and cannot be performed on site. This is where nanomedicine is playing a vital role. The discovery of new and innovative materials through the improvement in fabrication techniques has seen the establishment of an influx of novel antibacterial therapeutics and diagnostics. The goal of this review is to highlight the research that has been done through the implementation of nanomaterials and nanotechnologies for antibacterial medical therapeutic and diagnostic.

Relative deprivation between neighbouring wards is predictive of coronary heart disease mortality after adjustment for absolute deprivation of wards

Background The aims of this study were to assess whether deprivation inequality at small area level in England is associated with coronary heart disease (CHD) mortality rates and to assess whether this provides evidence of an association between area-level and individual-level risk.

Methods Mortality rates for all wards in England were calculated using all CHD deaths between 2001 and 2006. Ward-level deprivation was measured using the Carstairs Index. Deprivation inequality within local authorities (LAs) was measured by the IQR of deprivation for wards within the LA. Relative deprivation for wards was measured as the modulus of the difference between deprivation for the ward and average deprivation for all neighbouring wards.

Results Deprivation inequality within LAs was positively associated with CHD mortality rates per 100 000 (eg, all men β; 95% CI=2.7; 1.1 to 4.3) after adjustment for absolute deprivation (p<0.001 for all models). Relative deprivation for wards was positively associated with CHD mortality rates per 100 000 (eg, all men 1.4; 0.7 to 2.1) after adjustment for absolute deprivation (p<0.001 for all models). Subgroup analyses showed that relative deprivation was independently associated with CHD mortality rates in both affluent and deprived wards.

Conclusions Rich wards surrounded by poor areas have higher CHD mortality rates than rich wards surrounded by rich areas, and poor wards surrounded by rich areas have worse CHD mortality rates than poor wards surrounded by poor areas. Local deprivation inequality has a similar adverse impact on both rich and poor areas, supporting the hypothesis that income inequality of an area has an impact on individual-level health outcomes.

The societal benefits of reducing six behavioural risk factors : an economic modelling study from Australia

Background
A large proportion of disease burden is attributed to behavioural risk factors. However, funding for public health programs in Australia remains limited. Government and non-government organisations are interested in the productivity effects on society from reducing chronic diseases. We aimed to estimate the potential health status and economic benefits to society following a feasible reduction in the prevalence of six behavioural risk factors: tobacco smoking; inadequate fruit and vegetable consumption; high risk alcohol consumption; high body mass index; physical inactivity; and intimate partner violence.
Methods
Simulation models were developed for the 2008 Australian population. A realistic reduction in current risk factor prevalence using best available evidence with expert consensus was determined. Avoidable disease, deaths, Disability Adjusted Life Years (DALYs) and health sector costs were estimated. Productivity gains included workforce (friction cost method), household production and leisure time. Multivariable uncertainty analyses and correction for the joint effects of risk factors on health status were undertaken. Consistent methods and data sources were used.
Results
Over the lifetime of the 2008 Australian adult population, total opportunity cost savings of AUD2,334 million (95% Uncertainty Interval AUD1,395 to AUD3,347; 64% in the health sector) were found if feasible reductions in the risk factors were achieved. There would be 95,000 fewer DALYs (a reduction of about 3.6% in total DALYs for Australia); 161,000 less new cases of disease; 6,000 fewer deaths; a reduction of 5 million days in workforce absenteeism; and 529,000 increased days of leisure time.
Conclusions
Reductions in common behavioural risk factors may provide substantial benefits to society. For example, the total potential annual cost savings in the health sector represent approximately 2% of total annual health expenditure in Australia. Our findings contribute important new knowledge about productivity effects, including the potential for increased household and leisure activities, associated with chronic disease prevention. The selection of targets for risk factor prevalence reduction is an important policy decision and a useful approach for future analyses. Similar approaches could be applied in other countries if the data are available.

The economic benefits of reducing physical inactivity : an Australian example

Background: Physical inactivity has major impacts on health and productivity. Our aim was to estimate the health and economic benefits of reducing the prevalence of physical inactivity in the 2008 Australian adult population. The economic benefits were estimated as ‘opportunity cost savings’, which represent resources utilized in the treatment of preventable disease that are potentially available for re-direction to another purpose from fewer incident cases of disease occurring in communities.
Methods: Simulation models were developed to show the effect of a 10% feasible, reduction target for physical inactivity from current Australian levels (70%). Lifetime cohort health benefits were estimated as fewer incident cases of inactivity-related diseases; deaths; and Disability Adjusted Life Years (DALYs) by age and sex. Opportunity costs were estimated as health sector cost impacts, as well as paid and unpaid production gains and leisure impacts from fewer disease events associated with reduced physical inactivity. Workforce production gains were estimated by comparing surveyed participation and absenteeism rates of physically active and inactive adults, and valued using the friction cost approach. The impact of an improvement in health status on unpaid household production and leisure time were modeled from time use survey data, as applied to the exposed and non-exposed population subgroups and valued by suitable proxy. Potential costs associated with interventions to increase physical activity were not included. Multivariable uncertainty analyses and univariate sensitivity analyses were undertaken to provide information on the strength of the conclusions.
Results: A 10% reduction in physical inactivity would result in 6,000 fewer incident cases of disease, 2,000 fewer deaths, 25,000 fewer DALYs and provide gains in working days (114,000), days of home-based production (180,000) while conferring a AUD96 million reduction in health sector costs. Lifetime potential opportunity cost savings in workforce production (AUD12 million), home-based production (AUD71 million) and leisure-based production (AUD79 million) was estimated (total AUD162 million 95% uncertainty interval AUD136 million, AUD196 million).
Conclusions: Opportunity cost savings and health benefits conservatively estimated from a reduction in population-level physical inactivity may be substantial. The largest savings will benefit individuals in the form of unpaid production and leisure gains, followed by the health sector, business and government.

The epidemiology of ecstasy use and harms in New South Wales, Australia

Aims:This paper examines the epidemiology of ecstasy use and harm in Australia using multiple data sources.

Design: The data included (1) Australian Customs Service 3,4-methylenedioxymethamphetamine (MDMA) detections; (2) the National Drug Strategy Household and Australian Secondary Student Alcohol and Drug Surveys; (3) data from Australia's ecstasy and Related Drugs Reporting System; (4) the number of recorded police incidents for ecstasy possession and distribution collated by the N.S.W. Bureau of Crime Statistics and Research; (5) the number of calls to the Alcohol and Drug Information Service and Family Drug Support relating to ecstasy; (6) the Alcohol and Other Drug Treatment Services National Minimum Dataset on number of treatment episodes for ecstasy, and (7) N.S.W. Division of Analytical Laboratories toxicology data on number of deaths where MDMA was detected.

Findings: Recent ecstasy use among adults in the general population has increased, whereas among secondary students it has remained low and stable. The patterns of ecstasy consumption among regular ecstasy users have changed over time. Polydrug use and use for extended periods of time (>48 h) remain common among this group. Frequent ecstasy use is associated with a range of risk behaviours and other problems, which tend to be attributed to a number of drugs along with ecstasy. Few ecstasy users present for treatment for problems related to their ecstasy consumption.

Conclusions: Messages and interventions to reduce the risks associated with polydrug use and patterns of extended periods of use are clearly warranted. These messages should be delivered outside of traditional health care settings, as few of these users are engaged with such services.

Functional analysis of Plasmodium falciparum merozoite antigens : implications for erythrocyte invasion and vaccine development

Malaria is a major human health problem and is responsible for over 2 million deaths per year. It is caused by a number of species of the genus Plasmodium, and Plasmodium falciparum is the causative agent of the most lethal form. Consequently, the development of a vaccine against this parasite is a priority. There are a number of stages of the parasite life cycle that are being targeted for the development of vaccines. Important candidate antigens include proteins on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to manipulate the genome of Plasmodium species has enabled the construction of gain-of-function and loss-of-function mutants and provided new strategies to analyse the role of parasite proteins. This has provided new information on the role of merozoite antigens in erythrocyte invasion and also allows new approaches to address their potential as vaccine candidates.

Functional analysis of proteins involved in Plasmodium falciparum merozoite invasion of red blood cells

Plasmodium falciparum causes the most lethal form of malaria in humans and is responsible for over two million deaths per year. The development of a vaccine against this parasite is an urgent priority and potential protein targets include those on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to transfect P. falciparum has enabled the construction of gain-of-function and loss-of-function mutants and provided new strategies to analyse the role of parasite proteins. In this review, we describe the use of this technology to examine the role of merozoite antigens in erythrocyte invasion and to address their potential as vaccine candidates.

Modelling of potential food policy interventions in Fiji and Tonga and their impacts on noncommunicable disease mortality

Background: To compare the likely costs and benefits of a range of potential policy interventions in Fiji and Tonga targeted at diet-related noncommunicable diseases (NCDs), in order to support more evidence-based decision-making.

Method: A relatively simple and quick macro-simulation methodology was developed. Logic models were developed by local stakeholders and used to identify costs and dietary impacts of policy changes. Costs were confined to government costs, and excluded cost offsets. The best available evidence was combined with local data to model impacts on deaths from noncommunicable diseases over the lifetime of the target population. Given that the modelling necessarily entailed assumptions to compensate for gaps in data and evidence, use was made of probabilistic uncertainty analysis.

Results: Costs of implementing policy changes were generally low, with the exception of some requiring additional long-term staffing or construction activities. The most effective policy options in Fiji and Tonga targeted access to local produce and high-fat meats respectively, and were estimated to avert approximately 3% of diet-related NCD deaths in each population. Many policies had substantially lower benefits. Cost-effectiveness was higher for the low-cost policies. Similar policies produced markedly different results in the two countries.

Conclusion: Despite the crudeness of the method, the consistent modelling approach used across all the options, allowed reasonable comparisons to be made between the potential policy costs and impacts. This type of modelling can be used to support more evidence-based and informed decision-making about policy interventions and facilitate greater use of policy to achieve a reduction in NCDs.

Health outcomes associated with hormone therapy in Australian women

The risks and benefits of hormone therapy (HT) in the treatment of postmenopausal women remain controversial. In this population-based, observational study, we documented health outcomes among postmenopausal Australian women using HT. Women aged 60-80 years were recruited into the Geelong Osteoporosis Study 1994-7 and followed over a median period of 6.6 years. Mortality, and the development of vascular events, breast and colorectal cancers were documented for 67 HT-users and 521 non-users. Median duration of HT-use was 5.0 years (IQR 3.0-10.0). There was no excess in all-cause mortality associated with HT-use. Based on 92 deaths (six HT-users, 86 non-users), the adjusted odds ratio (OR) for all-cause mortality was 0.79 (95%CI 0.32-1.97). With 99 reports of vascular events (13 HTusers, 86 non-users), the adjusted OR for vascular events was 1.30 (95%CI 0.66-2.57). There were insufficient numbers of breast or colorectal cancer cases (21 breast cancer cases, all non-HT users; and 7 colorectal cancer cases, one HT-user and six non-users) to adequately calculate the risk associated with exposure to HT. Although the sample size was small, these results do not support an association between HT and mortality, despite a possible link between HT and increased risk of developing vascular disease.

What is the optimal level of population alcohol consumption for chronic disease prevention in England? Modelling the impact of changes in average consumption levels

Objective To estimate the impact of achieving alternative average population alcohol consumption levels on chronic disease mortality in England.

Design A macro-simulation model was built to simultaneously estimate the number of deaths from coronary heart disease, stroke, hypertensive disease, diabetes, liver cirrhosis, epilepsy and five cancers that would be averted or delayed annually as a result of changes in alcohol consumption among English adults. Counterfactual scenarios assessed the impact on alcohol-related mortalities of changing (1) the median alcohol consumption of drinkers and (2) the percentage of non-drinkers.

Data sources Risk relationships were drawn from published meta-analyses. Age- and sex-specific distributions of alcohol consumption (grams per day) for the English population in 2006 were drawn from the General Household Survey 2006, and age-, sex- and cause-specific mortality data for 2006 were provided by the Office for National Statistics.

Results The optimum median consumption level for drinkers in the model was 5 g/day (about half a unit), which would avert or delay 4579 (2544 to 6590) deaths per year. Approximately equal numbers of deaths from cancers and liver disease would be delayed or averted (∼2800 for each), while there was a small increase in cardiovascular mortality. The model showed no benefit in terms of reduced mortality when the proportion of non-drinkers in the population was increased.

Conclusions Current government recommendations for alcohol consumption are well above the level likely to minimise chronic disease. Public health targets should aim for a reduction in population alcohol consumption in order to reduce chronic disease mortality.

Modelling the health impact of environmentally sustainable dietary scenarios in the UK

BACKGROUND/OBJECTIVES:


Food is responsible for around one-fifth of all greenhouse gas (GHG) emissions from products consumed in the UK, the largest contributor of which is meat and dairy. The Committee on Climate Change have modelled the impact on GHG emissions of three dietary scenarios for food consumption in the UK. This paper models the impact of the three scenarios on mortality from cardiovascular disease and cancer.
SUBJECTS/METHODS:


A previously published model (DIETRON) was used. The three scenarios were parameterised by fruit and vegetables, fibre, total fat, saturated fat, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol and salt using the 2008 Family Food Survey. A Monte Carlo simulation generated 95% credible intervals.
RESULTS:


Scenario 1 (50% reduction in meat and dairy replaced by fruit, vegetables and cereals: 19% reduction in GHG emissions) resulted in 36 910 (30 192 to 43 592) deaths delayed or averted per year. Scenario 2 (75% reduction in cow and sheep meat replaced by pigs and poultry: 9% reduction in GHG emissions) resulted in 1999 (1739 to 2389) deaths delayed or averted. Scenario 3 (50% reduction in pigs and poultry replaced with fruit, vegetables and cereals: 3% reduction in GHG emissions) resulted in 9297 (7288 to 11 301) deaths delayed or averted.
CONCLUSION:


Modelled results suggest that public health and climate change dietary goals are in broad alignment with the largest results in both domains occurring when consumption of all meat and dairy products are reduced. Further work in real-life settings is needed to confirm these results.

Population-level changes to promote cardiovascular health

Background: Cardiovascular diseases (CVD) cause 1.8 million premature (<75 years) death annually in Europe. The majority of these deaths are preventable with the most efficient and cost-effective approach being on the population level. The aim of this position paper is to assist authorities in selecting the most adequate management strategies to prevent CVD.

Design and Methods: Experts reviewed and summarized the published evidence on the major modifiable CVD risk factors: food, physical inactivity, smoking, and alcohol. Population-based preventive strategies focus on fiscal measures (e.g. taxation), national and regional policies (e.g. smoke-free legislation), and environmental changes (e.g. availability of alcohol).

Results: Food is a complex area, but several strategies can be effective in increasing fruit and vegetables and lowering intake of salt, saturated fat, trans-fats, and free sugars. Tobacco and alcohol can be regulated mainly by fiscal measures and national policies, but local availability also plays a role. Changes in national policies and the built environment will integrate physical activity into daily life.

Conclusion: Societal changes and commercial influences have led to the present unhealthy environment, in which default option in life style increases CVD risk. A challenge for both central and local authorities is, therefore, to ensure healthier defaults. This position paper summarizes the evidence and recommends a number of structural strategies at international, national, and regional levels that in combination can substantially reduce CVD.

The influence of hip circumference on the relationship between abdominal obesity and mortality

Background Higher waist circumference and lower hip circumference are both associated with increased cardiovascular disease (CVD) risk, despite being directly correlated. The real effects of visceral obesity may therefore be underestimated when hip circumference is not fully taken into account. We hypothesized that adding waist and hip circumference to traditional risk factors would significantly improve CVD risk prediction.

Methods In a population-based survey among South Asian and African Mauritians (n = 7978), 1241 deaths occurred during 15 years of follow-up. In a model that included variables used in previous CVD risk calculations (a Framingham-type model), the association between waist circumference and mortality was examined before and after adjustment for hip circumference. The percentage with an increase in estimated 10-year cumulative mortality of >25% and a decrease of >20% after waist and hip circumference were added to the model was calculated.

Results Waist circumference was strongly related to mortality only after adjustment for hip circumference and vice versa. Adding waist and hip circumference to a Framingham-type model increased estimated 10-year cumulative CVD mortality by >25% for 23.7% of those who died and 15.7% of those censored. Cumulative mortality decreased by >20% for 4.5% of those who died and 14.8% of those censored.

Conclusions The effect of central obesity on mortality risk is seriously underestimated without adjustment for hip circumference. Adding waist and hip circumference to a Framingham-type model for CVD mortality substantially increased predictive power. Both may be important inclusions in CVD risk prediction models.