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The politics and science of health and disease remain contested terrain among scientists, health practitioners, policy makers, industry, communities, and the public. Stakeholders in disputes about illnesses or conditions disagree over their fundamental causes as well as how they should be treated and prevented. This thought-provoking book crosses disciplinary boundaries by engaging with both public health policy and social science, asserting that science, activism, and policy are not separate issues and showing how the contribution of environmental factors in disease is often overlooked.

The long search for the environmental trigger of the endemic pemphigus foliaceus (EPF, fogo selvagem) has not yet resulted in any tangible findings. Here, we searched for genetic associations and the differential expression of host genes involved in early viral infections and innate antiviral defense. Genetic variants could alter the structure, expression sites, or levels of the gene products, impacting their functions. By analyzing 3063 variants of 166 candidate genes in 227 EPF patients and 194 controls, we found 12 variants within 11 genes associated with differential susceptibility (p < 0.005) to EPF. The products of genes TRIM5, TPCN2, EIF4E, EIF4E3, NUP37, NUP50, NUP88, TPR, USP15, IRF8, and JAK1 are involved in different mechanisms of viral control, for example, the regulation of viral entry into the host cell or recognition of viral nucleic acids and proteins. Only two of nine variants were also associated in an independent German cohort of sporadic PF (75 patients, 150 controls), aligning with our hypothesis that antiviral host genes play a major role in EPF due to a specific virus–human interaction in the endemic region. Moreover, CCL5, P4HB, and APOBEC3G mRNA levels were increased (p < 0.001) in CD4+ T lymphocytes of EPF patients. Because there is limited or no evidence that these genes are involved in autoimmunity, their crucial role in antiviral responses and the associations that we observed support the hypothesis of a viral trigger for EPF, presumably a still unnoticed flavivirus. This work opens new frontiers in searching for the trigger of EPF, with the potential to advance translational research that aims for disease prevention and treatment.

Bolesti uzrokovane čimbenicima okoliša obuhvaćaju poremećaje koji su uzrokovani različitim okolišnim čimbenicima te promjenama ponašanja stanovnika. Urbana područja diljem svijeta suočavaju se s velikim brojem čimbenika okoliša koji utječu na javno zdravlje, kao što su onečišćenje zraka, voda, buka, polutanti, gustoća prometa, prenapučenost u gradovima, smanjenje zelenih površina, itd. Pravovremeno otkrivanje i kvantifikacija rizičnih čimbenika okoliša, koji utječu na javno zdravlje, veoma je važna jer svaka intervencija na ovom području može smanjiti rizik od obolijevanja i poboljšati zdravlje stanovništva. Unutarstanične matriks metaloproteinaze (MMPs) lokalizirane su u različitim odjeljcima unutar stanice uključujući citosol, sarkomeru, mitohondrije i jezgru. Intracelularne MMPs pridonose patogenezi različitih bolesti. Cilj ovog preglednog rada je istražiti uloge matriks metaloproteinaza u razvoju bolesti respiracijskog sustava uzrokovanih čimbenicima okoliša te važnost njihovog određivanja kao potencijalnih pokazatelja ranih tkivnih oštećenja u ljudi. MMP su se dokazale, uz imunološki status, kao dobar biljeg za praćenje bolesti uzrokovanih čimbenicima okoliša. Osim u dijagnostici i monitoringu bolesti uzrokovanih čimbenicima okoliša, MMPs i njihovi tkivni inhibitori (TIMP, engl. tissue inhibitor of metalloproteinase) predstavljaju potencijalni cilj liječenja. The incidence of environmental diseases, especially in highly developed industrial countries, has increased by more than 30% in the last few decades. These diseases represent a burden for both the individual and public health. Many of them (asthma, allergic rhinitis, chronic obstructive pulmonary disease, cardiovascular diseases) are a major public health problem, and it is necessary to identify harmful environmental factors, determine the mechanisms of their action, find adequate markers for early diagnosis and disease monitoring. By doing that better preventive and therapeutic effects can be achieved. In order to prevent the development of environmental diseases and to preserve environmental health in addition to knowing mechanisms by which harmful compounds enter the ecosystem (e.g. unintentional discharge, waste disposal, operation of industrial plants, transport) toxic kinetics is also important, i.e. absorption, biological conversion, distribution and excretion of harmful compounds and their metabolites from the organism. Intracellular matrix metalloproteinases (MMPs) are localized in various compartments within the cell including the cytosol, sarcomere, mitochondria, and nucleus. Intracellular MMPs contribute to the pathogenesis of various diseases. These include diseases with altered immune responses, cardiovascular diseases, respiratory diseases, inflammation, renal disorders, and malignant diseases. MMPs have antiviral and bactericidal effects and can act intracellularly through protease-dependent mechanisms. In addition to their immune status they are proven to be a good marker for monitoring environmental diseases. In addition to diagnosing and monitoring environmental diseases, MMPs and their tissue inhibitors (TIMPs) represent a potential treatment goal.

Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk–outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk–outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk–outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95% uncertainty interval [UI] 9·51–12·1) deaths (19·2% [16·9–21·3] of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12–9·31) deaths (15·4% [14·6–16·2] of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253–350) DALYs (11·6% [10·3–13·1] of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0–9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10–24 years, alcohol use for those aged 25–49 years, and high systolic blood pressure for those aged 50–74 years and 75 years and older. Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Bill & Melinda Gates Foundation.

Contamination of public parks by dogs is a potential source of conflict among park users, causing “tragedy of the commons” problems. Besides the social conflict, feces can pose serious health risks to both dogs and humans. In this study we analyzed the extent and patterns of the distribution of dog feces in the urban parks of the City of Calgary. We collected dog feces from randomly selected locations in the urban parks. The average density of dog feces by the different dog leash policies of the parks and the distribution pattern of the fecal density within the parks were assessed, and the total contamination of the public parks for the entire city was estimated. We found off-leash parks to be significantly more contaminated than other types of parks. We estimated 127.23 g/ha of dog feces are left unpicked in city parks in total every week. Dog feces were found more often and in greater amount in off-leash parks, and near park entrances and parking lots, than in on-leash parks and away from the park entrances. These results suggest that public park visitors, especially those visiting off-leash parks, are likely to be exposed to large amounts of dog feces. Designation of parks as on-leash and educating dog-owners may be an effective approach for reducing the fecal contamination.

Many areas of the Campania region of Italy are more frequently at risk of neoplastic diseases due to environmental factors. However, the results of epidemiological studies, although numerous and detailed, do not explain tumor pathogenesis mechanisms in relation to the contribution of exposure to environmental pollutants. The Oncological Biobank of the G. Pascale Foundation (BBI) centralizes the collection and storage of biomaterials, both healthy and pathological human tissues, from urban and extra-urban areas of Naples, associating them with clinicopathological characteristics (type of tumor, histological type, grading, immunohistochemical and molecular profile, etc.). Geo-location of tumor samples is made by an IT platform in which demographic and clinical data are systematically uploaded. For the extra-urban areas of Naples, our experience of tumor sample geolocation highlighted cancer types with high impact of environmental pollutants as being lung, gastric and bladder cancer. In this mini-review, we underline that the possibility of specifically selecting tumor samples in circumscribed territories may allow targeted studies to verify potential connections between environmental factors and cancer. Moreover, the collection of biological fluids (serum, saliva, urine) from healthy individuals from specific areas may be a useful tool for the research of specific genetic polymorphisms linked to individual susceptibility.

Blood pressure (BP) exhibits seasonal variation, with an elevation of daytime BP in winter and an elevation of nighttime BP in summer. The wintertime elevation of daytime BP is largely attributable to cold temperatures. The summertime elevation of nighttime BP is not due mainly to temperature; rather, it is considered to be related to physical discomfort and poor sleep quality due to the summer weather. The winter elevation of daytime BP is likely to be associated with the increased incidence of cardiovascular disease (CVD) events in winter compared to other seasons. The suppression of excess seasonal BP changes, especially the wintertime elevation of daytime BP and the summertime elevation of nighttime BP, would contribute to the prevention of CVD events. Herein, we review the literature on seasonal variations in BP, and we recommend the following measures for suppressing excess seasonal BP changes as part of a regimen to manage hypertension: (1) out-of-office BP monitoring, especially home BP measurements, throughout the year to evaluate seasonal variations in BP; (2) the early titration and tapering of antihypertensive medications before winter and summer; (3) the optimization of environmental factors such as room temperature and housing conditions; and (4) the use of information and communication technology-based medicine to evaluate seasonal variations in BP and provide early therapeutic intervention. Seasonal BP variations are an important treatment target for the prevention of CVD through the management of hypertension, and further research is necessary to clarify these variations.

Just Doctoring draws the doctor-patient relationship out of the consulting room and into the middle of the legal and political arenas where it more and more frequently appears. Traditionally, medical ethics has focused on the isolated relationship of physician to patient in a setting that has left the physician virtually untouched by market constraints or government regulation. Arguing that changes in health care institutions and legal attention to patient rights have made conventional approaches obsolete, Troyen Brennan points the way to a new, more aware and engaged medical ethics. The medical profession is no longer isolated, even theoretically, from the liberal, market-dominated state. Old ideas of physician beneficence and altruism must make way for a justice-based medical ethics, assuming a relationship between equals more compatible with liberal political philosophy. Brennan offers clinical examples of many of today's most challenging medical problems--from informed consent to care rationing and the repercussions of the HIV epidemic--and gives his recommendation for a new ethical perspective. This lively and controversial plea for a rethinking of medical ethics goes right to the heart of medical care at the end of the twentieth century. This title is part of UC Press's Voices Revived program, which commemorates University of California Press's mission to seek out and cultivate the brightest minds and give them voice, reach, and impact. Drawing on a backlist dating to 1893, Voices Revived makes high-quality, peer-reviewed scholarship accessible once again using print-on-demand technology. This title was originally published in 1991. Many titles in the Voices Revived program are also newly available as ebooks, offered at a discounted price to support wider access to scholarly work.

In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Bill & Melinda Gates Foundation.

A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases. In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex. Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017–19 vs 2000–02 1·04 [95% CI 1·00–1·09]). The largest increases were seen in coeliac disease (2·19 [2·05–2·35]), Sjogren's syndrome (2·09 [1·84–2·37]), and Graves' disease (2·07 [1·92–2·22]); pernicious anaemia (0·79 [0·72–0·86]) and Hashimoto's thyroiditis (0·81 [0·75–0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64–1·81]), rheumatoid arthritis (1·52 [1·45–1·59]), Graves' disease (1·36 [1·30–1·43]), and systemic lupus erythematosus (1·35 [1·25–1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3–40·7]), coeliac disease (28·4 [25·2–32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8–14·9] and Graves' disease 6·7 [5·1–8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases. Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. Research Foundation Flanders.