Hepcidin and the Iron-Infection Axis Drakesmith, Hal; Prentice, Andrew M.
Science (American Association for the Advancement of Science),
11/2012, Letnik:
338, Številka:
6108
Journal Article
Recenzirano
Iron lies at the center of a battle for nutritional resource between higher organisms and their microbial pathogens. The iron status of the human host affects the pathogenicity of numerous infections ...including malaria, HIV-1, and tuberculosis. Hepcidin, an antimicrobial-like peptide hormone, has emerged as the master regulator of iron metabolism. Hepcidin controls the absorption of dietary iron and the distribution of iron among cell types in the body, and its synthesis is regulated by both iron and innate immunity. We describe how hepcidin integrates signals from diverse physiological inputs, forming a key molecular bridge between iron trafficking and response to infection.
Parental environmental factors, including diet, body composition, metabolism, and stress, affect the health and chronic disease risk of people throughout their lives, as captured in the Developmental ...Origins of Health and Disease concept. Research across the epidemiological, clinical, and basic science fields has identified the period around conception as being crucial for the processes mediating parental influences on the health of the next generation. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune, and neurological morbidities, often termed developmental programming. We review periconceptional induction of disease risk from four broad exposures: maternal overnutrition and obesity; maternal undernutrition; related paternal factors; and the use of assisted reproductive treatment. Studies in both humans and animal models have demonstrated the underlying biological mechanisms, including epigenetic, cellular, physiological, and metabolic processes. We also present a meta-analysis of mouse paternal and maternal protein undernutrition that suggests distinct parental periconceptional contributions to postnatal outcomes. We propose that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.
An analysis of early growth patterns in children from 54 resource-poor countries in Africa and Southeast Asia shows a rapid falloff in the height-for-age z score during the first 2 y of life and no ...recovery until ≥5 y of age. This finding has focused attention on the period −9 to 24 mo as a window of opportunity for interventions against stunting and has garnered considerable political backing for investment targeted at the first 1000 d. These important initiatives should not be undermined, but the objective of this study was to counteract the growing impression that interventions outside of this period cannot be effective. We illustrate our arguments using longitudinal data from the Consortium of Health Oriented Research in Transitioning collaboration (Brazil, Guatemala, India, Philippines, and South Africa) and our own cross-sectional and longitudinal growth data from rural Gambia. We show that substantial height catch-up occurs between 24 mo and midchildhood and again between midchildhood and adulthood, even in the absence of any interventions. Longitudinal growth data from rural Gambia also illustrate that an extended pubertal growth phase allows very considerable height recovery, especially in girls during adolescence. In light of the critical importance of maternal stature to her children's health, our arguments are a reminder of the importance of the more comprehensive UNICEF/Sub-Committee on Nutrition Through the Life-Cycle approach. In particular, we argue that adolescence represents an additional window of opportunity during which substantial life cycle and intergenerational effects can be accrued. The regulation of such growth is complex and may be affected by nutritional interventions imposed many years previously.
Undernutrition in both its acute and chronic forms (wasting and stunting) is strongly inversely correlated with the wealth of nations. Consequently, as many low-and middle-income countries (LMICs) ...achieve economic advancement and pass through the so-called “nutrition transition,” their rates of undernutrition decline. Many countries successfully achieved the Millennium Development Goal of halving undernutrition and whole continents have been transformed in recent decades. The exception is Africa where the slower rates of decline in the prevalence of undernutrition has been overtaken by population growth so that the absolute number of stunted children is rising. In many regions, economic transition is causing a rapid increase in the number of overweight and obese people. The rapidity of this rise is such that many nations bear the simultaneous burdens of under-and overnutrition; termed the “double burden” of malnutrition. This double burden, accompanied as it is by the unfinished agenda of high levels of infectious diseases, is crippling the health systems of many LMICs and thus requires urgent attention. Although the prognosis looks threatening for many poor countries, they have the advantage of being able to learn from the mistakes made by other nations that have passed through the transition before them. Concerted action across many arms of government would achieve huge future dividends in health and wealth for any nations that can grasp the challenge.
The median age of prostate cancer diagnosis is 66 years, and the median age of men who die of the disease is eighty years. The public health impact of prostate cancer is already substantial and, ...given the rapidly ageing world population, can only increase. In this context, the International Society of Geriatric Oncology (SIOG) Task Forces have, since 2010, been developing guidelines for the management of senior adults with prostate cancer.
Since prostate cancer and geriatric oncology are both rapidly evolving fields, a new multidisciplinary Task Force was formed in 2018 to update SIOG recommendations, principally on health status screening tools and treatment. The task force reviewed pertinent articles published between June 2016 and June 2018 and abstracts from European Association of Urology (EAU), European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and American Society of Clinical Oncology Genito-urinary (ASCO GU) meetings over the same period, using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments and advanced disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus.
The 2019 consensus is that men aged 75 years and older with prostate cancer should be managed according to their individual health status, and not according to age. Based on available rapid health screening tools, geriatric evaluation and geriatric interventions, the Task Force recommends that patients are classified according to health status into three groups: (1) 'healthy' or 'fit' patients should have the same treatment options as younger patients; (2) 'vulnerable' patients are candidates for geriatric interventions which-if successful-may make it appropriate for them to receive standard treatment and (3) 'frail' patients with major impairments who should receive adapted or palliative treatment. The 2019 SIOG Task Force recommendations also discuss prospects and unmet needs for health status evaluation in everyday practice in older patients with prostate cancer.
Thirty years ago international nutritionists were focussing on childhood malnutrition, the ‘protein gap’ and how to feed the world's burgeoning population, and medical services in the developing ...world were concentrated on the fight against infectious diseases. Today the World Health Organization (WHO) finds itself needing to deal with the new pandemic of obesity and its accompanying non-communicable diseases (NCDs) while the challenge of childhood malnutrition has far from disappeared, TB and malaria rates are escalating, and the scourge of AIDS has emerged. This has created a ‘double burden’ of disease that threatens to overwhelm the health services of many resource-poor countries. WHO warns that the greater future burden of obesity and diabetes will affect developing countries, and the projected numbers of new cases of diabetes run into the hundreds of millions within the next 2 decades. The obesity pandemic originated in the US and crossed to Europe and the world's other rich nations before, remarkably, it penetrated even the world's poorest countries especially in their urban areas. The pandemic is transmitted through the vectors of subsidized agriculture and multinational companies providing cheap, highly refined fats, oils, and carbohydrates, labour-saving mechanized devices, affordable motorized transport, and the seductions of sedentary pastimes such as television. This paper briefly reviews these macro-environmental trends as well as considering some of the socio-behavioural influences on weight gain in traditional societies. It concludes, pessimistically, that the pandemic will continue to spread for the foreseeable future, and that, apart from educational campaigns, the governments and health services of poor countries will have few effective public health levers with which they can try to arrest the trend.
OPTN/SRTR 2019 Annual Data Report: Kidney Hart, A.; Lentine, K. L.; Smith, J. M. ...
American journal of transplantation,
February 2021, 2021-02-00, 20210201, Letnik:
21, Številka:
S2
Journal Article
Recenzirano
Odprti dostop
Despite the ongoing severe shortage of available kidney grafts relative to candidates in need, data from 2019 reveal some promising trends. After remaining relatively stagnant for many years, the ...number of kidney transplants has increased each year since 2015, reaching the highest annual count to date of 24,273 in 2019. The number of patients waiting for a kidney transplant in the United States was relatively stable, despite an increase in the number of new candidates added in 2019 and a decrease in patients removed from the waiting list owing to death or deteriorating medical condition. However, these encouraging trends are tempered by ongoing challenges. Nationwide, only a quarter of waitlisted patients receive a deceased‐donor kidney transplant within 5 years, and this proportion varies dramatically by donation service area, from 15.5% to 67.8%. The non‐utilization (discard) rate of recovered organs remains at 20.1%, despite adramatic decline in the discard of organs from hepatitis C‐positive donors. Non‐utilization rates remain particularly high for Kidney Donor Profile Index ≥85% kidneys and kidneys from which a biopsy specimen was obtained. While the number of living‐donor transplants increased again in 2019, only a small proportion of the waiting list receives living‐donor transplants each year, and racial disparities in living‐donor transplant access persist. As both graft and patient survival continue to improve incrementally, the total number of living kidney transplant recipients with a functioning graft is anticipated to exceed 250,000 in the next 1‐2 years. Over the past decade, the total number of pediatric kidney transplants performed has remained stable. Despite numerous efforts, living donor kidney transplant remains low among pediatric recipients with continued racial disparities among recipients. Congenital anomalies of the kidney and urinary tract remain the leading cause of kidney disease. While most deceased donor recipients receive a kidney from a donor with KDPI less than 35%, the majority of pediatric recipients had four or more HLA mismatches. Graft survival continues to improve with superior outcomes for living donor recipients.
Adolescence is the period of development that begins at puberty and ends in early adulthood. Most commonly, adolescence is divided into three developmental periods: early adolescence (10–14 years of ...age), late adolescence (15–19 years of age), and young adulthood (20–24 years of age). Adolescence is marked by physical and sexual maturation, social and economic independence, development of identity, acquisition of skills needed to carry out adult relationships and roles, and the capacity for reasoning. Adolescence is characterized by a rapid pace of growth that is second only to that of infancy. Nutrition and the adolescent transition are closely intertwined, since eating patterns and behaviors are influenced by many factors, including peer influences, parental modeling, food availability, food preferences, cost, convenience, personal and cultural beliefs, mass media, and body image. Here, we describe the physiology, metabolism, and nutritional requirements for adolescents and pregnant adolescents, as well as nutrition‐related behavior and current trends in adolescent nutrition. We conclude with thoughts on the implications for nutrition interventions and priority areas that would require further investigation.
Social changes in the 20th century resulted in substantial reductions in the prevalence of breastfeeding in many countries but especially in those with high and increasing wealth. Concerns about this ...decline prompted widespread research to quantify the benefits of breastfeeding and the mechanisms by which it exerts protective effects for mothers and children. Pro-breastfeeding advocacy resulted in the WHO International Code of Marketing of Breastmilk Substitutes in 1981 and the Innocenti Declaration on Breastfeeding in 1990, which, together with numerous other initiatives, have helped to turn the tide.
A tranche of recent meta-analyses of dozens of individual studies provide very strong evidence that breastfeeding has substantial benefits to babies, infants, and young children. The benefits and strengths of association vary according to the background environmental and hygiene conditions in different settings. In low-income settings, the chief measurable benefits for the child are in respect of reductions in diarrhea and respiratory infections, and in mortality. In high-income settings, breastfeeding protects against otitis media, likely protects against type 2 diabetes and overweight and obesity, and possibly protects against type 1 diabetes. It likely improves IQ by 2-3 percentage points. In mothers, breastfeeding reduces a mother's likelihood of breast and ovarian cancers. Feeding these data into the Lives Saved Tool suggests that these benefits could prevent 823,000 deaths in children and 22,000 among women.
The etiologic relationship between wasting and stunting is poorly understood, largely because of a lack of high-quality longitudinal data from children at risk of undernutrition.
The aim of this ...study was to describe the interrelationships between wasting and stunting in children aged <2 y.
This study involved a retrospective cohort analysis, based on growth-monitoring records spanning 4 decades from clinics in rural Gambia. Anthropometric data collected at scheduled infant welfare clinics were converted to z scores, comprising 64,342 observations on 5160 subjects (median: 12 observations per individual). Children were defined as “wasted” if they had a weight-for-length z score <–2 against the WHO reference and “stunted” if they had a length-for-age z score <–2.
Levels of wasting and stunting were high in this population, peaking at approximately (girls–boys) 12–18% at 10–12 months (wasted) and 37–39% at 24 mo of age (stunted). Infants born at the start of the annual wet season (July–October) showed early growth faltering in weight-for-length z score, putting them at increased risk of subsequent stunting. Using time-lagged observations, being wasted was predictive of stunting (OR: 3.2; 95% CI: 2.7, 3.9), even after accounting for current stunting. Boys were more likely to be wasted, stunted, and concurrently wasted and stunted than girls, as well as being more susceptible to seasonally driven growth deficits.
We provide evidence that stunting is in part a biological response to previous episodes of being wasted. This finding suggests that stunting may represent a deleterious form of adaptation to more overt undernutrition (wasting). This is important from a policy perspective as it suggests we are failing to recognize the importance of wasting simply because it tends to be more acute and treatable. These data suggest that stunted children are not just short children but are children who earlier were more seriously malnourished and who are survivors of a composite process.