Cardiovascular screening to reduce the burden from cardiovascular disease: microsimulation study to quantify policy options.

OBJECTIVES:  To estimate the potential impact of universal screening for primary prevention of cardiovascular disease (National Health Service Health Checks) on disease burden and socioeconomic inequalities in health in England, and to compare universal screening with alternative feasible strategies. DESIGN:  Microsimulation study of a close-to-reality synthetic population. Five scenarios were considered: baseline scenario, assuming that current trends in risk factors will continue in the future; universal screening; screening concentrated only in the most deprived areas; structural population-wide intervention; and combination of population-wide intervention and concentrated screening. SETTING:  Synthetic population with similar characteristics to the community dwelling population of England. PARTICIPANTS:  Synthetic people with traits informed by the health survey for England. MAIN OUTCOME MEASURE:  Cardiovascular disease cases and deaths prevented or postponed by 2030, stratified by fifths of socioeconomic status using the index of multiple deprivation. RESULTS:  Compared with the baseline scenario, universal screening may prevent or postpone approximately 19 000 cases (interquartile range 11 000-28 000) and 3000 deaths (-1000-6000); concentrated screening 17 000 cases (9000-26 000) and 2000 deaths (-1000-5000); population-wide intervention 67 000 cases (57 000-77 000) and 8000 deaths (4000-11 000); and the combination of the population-wide intervention and concentrated screening 82 000 cases (73 000-93 000) and 9000 deaths (6000-13 000). The most equitable strategy would be the combination of the population-wide intervention and concentrated screening, followed by concentrated screening alone and the population-wide intervention. Universal screening had the least apparent impact on socioeconomic inequalities in health. CONCLUSIONS:  When primary prevention strategies for reducing cardiovascular disease burden and inequalities are compared, universal screening seems less effective than alternative strategies, which incorporate population-wide approaches. Further research is needed to identify the best mix of population-wide and risk targeted CVD strategies to maximise cost effectiveness and minimise inequalities.

The effects of maximising the UK's tobacco control score on inequalities in smoking prevalence and premature coronary heart disease mortality: a modelling study.

BACKGROUND: Smoking is more than twice as common among the most disadvantaged socioeconomic groups in England compared to the most affluent and is a major contributor to health-related inequalities. The United Kingdom (UK) has comprehensive smoking policies in place: regular tax increases; public information campaigns; on-pack pictorial health warnings; advertising bans; cessation; and smoke-free areas. This is confirmed from its high Tobacco Control Scale (TCS) score, an expert-developed instrument for assessing the strength of tobacco control policies. However, room remains for improvement in tobacco control policies. Our aim was to evaluate the cumulative effect on smoking prevalence of improving all TCS components in England, stratified by socioeconomic circumstance. METHODS: Effect sizes and socioeconomic gradients for all six types of smoking policy in the UK setting were adapted from systematic reviews, or if not available, from primary studies. We used the IMPACT Policy Model to link predicted changes in smoking prevalence to changes in premature coronary heart disease (CHD) mortality for ages 35-74. Health outcomes with a time horizon of 2025 were stratified by quintiles of socioeconomic circumstance. RESULTS: The model estimated that improving all smoking policies to achieve a maximum score on the TCS might reduce smoking prevalence in England by 3% (95% Confidence Interval (CI): 1-4%), from 20 to 17% in absolute terms, or by 15% in relative terms (95% CI: 7-21%). The most deprived quintile would benefit more, with absolute reductions from 31 to 25%, or a 6% reduction (95% CI: 2-7%). There would be some 3300 (95% CI: 2200-4700) fewer premature CHD deaths between 2015-2025, a 2% (95% CI: 1.4-2.9%) reduction. The most disadvantaged quintile would benefit more, reducing absolute inequality of CHD mortality by about 4 % (95% CI: 3-9%). CONCLUSIONS: Further, feasible improvements in tobacco control policy could substantially improve population health, and reduce health-related inequalities in England.

Future trends and inequalities in premature coronary deaths in England: Modelling study.

BACKGROUND: Coronary heart disease (CHD) is a major cause of premature mortality, particularly in deprived groups. Might recent declines in overall mortality obscure different rates of decline among social strata, creating potentially misleading views on inequalities? METHODS: We used a Bayesian analysis of an age-period-cohort model for the English population. We projected age-specific premature CHD mortality (ages 35-74) by gender and area-based deprivation status for the period 2007-2035, using 1982-2006 as the input. Deprivation status was measured by Index of Multiple Deprivation quintiles, which aggregate seven types of deprivation, including health and income. We analysed inequality in premature CHD mortality. We investigated the annual changes in inequality and the contributions of changes in each IMDQ to the overall annual changes, using both absolute (probability) and relative (logit) scales. We quantified inequality using the statistical variance in the probability of premature death among deprivation quintiles. RESULTS: The overall premature CHD mortality trends conceal marked heterogeneities. Our models predict more rapid declines in premature CHD mortality for the most affluent quintiles than for the most deprived (annualized rate of decline 2006-2025, 7.5% [95% Credible Interval 4.3-10.5%] versus 5.4% [2.2-8.7%] for men, and 6.3% [3.0-9.9%] versus 5.9% [1.5-10.8%] for women). For men, the posterior probability that the rate of decline is greater for the most affluent was 82%. Variance in premature CHD mortality across deprivation quintiles was projected to decrease by approximately 81% [28-95%] among men and by 89% [30-99%] among women. This decrease was particularly driven by the most deprived groups due to their higher premature death rates. However, relative inequality was projected to rise by 93% among men [81-125%] and rise by 13% [-25-58%] among women. These increases are also mostly influenced by the most deprived, reflecting their slower declines in premature deaths. CONCLUSIONS: Overall, premature coronary death rates in England continue to decline steeply. Absolute inequalities are decreasing, reflecting declines in the high premature mortality in deprived groups. However, relative inequalities are projected to widen further, reflecting slower mortality declines in the most deprived groups. More aggressive and progressive prevention policies are urgently needed.

Potential of trans fats policies to reduce socioeconomic inequalities in mortality from coronary heart disease in England: cost effectiveness modelling study.

OBJECTIVES: To determine health and equity benefits and cost effectiveness of policies to reduce or eliminate trans fatty acids from processed foods, compared with consumption remaining at most recent levels in England. DESIGN: Epidemiological modelling study. SETTING: Data from National Diet and Nutrition Survey, Low Income Diet and Nutrition Survey, Office of National Statistics, and health economic data from other published studies PARTICIPANTS: Adults aged ≥25, stratified by fifths of socioeconomic circumstance. INTERVENTIONS: Total ban on trans fatty acids in processed foods; improved labelling of trans fatty acids; bans on trans fatty acids in restaurants and takeaways. MAIN OUTCOME MEASURES: Deaths from coronary heart disease prevented or postponed; life years gained; quality adjusted life years gained. Policy costs to government and industry; policy savings from reductions in direct healthcare, informal care, and productivity loss. RESULTS: A total ban on trans fatty acids in processed foods might prevent or postpone about 7200 deaths (2.6%) from coronary heart disease from 2015-20 and reduce inequality in mortality from coronary heart disease by about 3000 deaths (15%). Policies to improve labelling or simply remove trans fatty acids from restaurants/fast food could save between 1800 (0.7%) and 3500 (1.3%) deaths from coronary heart disease and reduce inequalities by 600 (3%) to 1500 (7%) deaths, thus making them at best half as effective. A total ban would have the greatest net cost savings of about £265m (€361m, $415m) excluding reformulation costs, or £64m if substantial reformulation costs are incurred outside the normal cycle. CONCLUSIONS: A regulatory policy to eliminate trans fatty acids from processed foods in England would be the most effective and equitable policy option. Intermediate policies would also be beneficial. Simply continuing to rely on industry to voluntary reformulate products, however, could have negative health and economic outcomes.

The Health Equity and Effectiveness of Policy Options to Reduce Dietary Salt Intake in England: Policy Forecast.

BACKGROUND: Public health action to reduce dietary salt intake has driven substantial reductions in coronary heart disease (CHD) over the past decade, but avoidable socio-economic differentials remain. We therefore forecast how further intervention to reduce dietary salt intake might affect the overall level and inequality of CHD mortality. METHODS: We considered English adults, with socio-economic circumstances (SEC) stratified by quintiles of the Index of Multiple Deprivation. We used IMPACTSEC, a validated CHD policy model, to link policy implementation to salt intake, systolic blood pressure and CHD mortality. We forecast the effects of mandatory and voluntary product reformulation, nutrition labelling and social marketing (e.g., health promotion, education). To inform our forecasts, we elicited experts' predictions on further policy implementation up to 2020. We then modelled the effects on CHD mortality up to 2025 and simultaneously assessed the socio-economic differentials of effect. RESULTS: Mandatory reformulation might prevent or postpone 4,500 (2,900-6,100) CHD deaths in total, with the effect greater by 500 (300-700) deaths or 85% in the most deprived than in the most affluent. Further voluntary reformulation was predicted to be less effective and inequality-reducing, preventing or postponing 1,500 (200-5,000) CHD deaths in total, with the effect greater by 100 (-100-600) deaths or 49% in the most deprived than in the most affluent. Further social marketing and improvements to labelling might each prevent or postpone 400-500 CHD deaths, but minimally affect inequality. CONCLUSIONS: Mandatory engagement with industry to limit salt in processed-foods appears a promising and inequality-reducing option. For other policy options, our expert-driven forecast warns that future policy implementation might reach more deprived individuals less well, limiting inequality reduction. We therefore encourage planners to prioritise equity.

Hypocholesterolemic Effect and In Vitro Pancreatic Lipase Inhibitory Activity of an Opuntia ficus-indica Extract.

Cholesterol control is fundamental for prevention of cardiovascular disorders. In this work, the hypocholesterolemic activity of an aqueous Opuntia ficus-indica extract (AOE) was tested in triton-induced mice. The inhibitory activity on pancreatic lipase enzyme was evaluated in vitro by the same extract. Furthermore, polyphenol content of the extract was evaluated. Hypercholesterolemia was induced in three groups of mice by intraperitoneal administration of Triton WR-1339. After induction of hypercholesterolemia, the groups were treated with an AOE (500 mg/kg) and saline solution and the positive control group with orlistat, respectively. Cholesterol levels were measured 24 h later in peripheral blood. The levels of blood cholesterol after administration of AOE significantly decreased compared to negative control. The inhibitory activity of AOE on pancreatic lipase enzyme was evaluated at concentrations from 60 to 1000 µg/mL. The AOE inhibited the pancreatic lipase with an IC50 = 588.5 µg/mL. The AOE had a high content of polyphenolic compounds. These results show that AOE is able to prevent hypercholesterolemia by pancreatic lipase inhibition, in part due to its polyphenolic compounds.

Are interventions to promote healthy eating equally effective for all? Systematic review of socioeconomic inequalities in impact.

BACKGROUND: Interventions to promote healthy eating make a potentially powerful contribution to the primary prevention of non communicable diseases. It is not known whether healthy eating interventions are equally effective among all sections of the population, nor whether they narrow or widen the health gap between rich and poor. We undertook a systematic review of interventions to promote healthy eating to identify whether impacts differ by socioeconomic position (SEP). METHODS: We searched five bibliographic databases using a pre-piloted search strategy. Retrieved articles were screened independently by two reviewers. Healthier diets were defined as the reduced intake of salt, sugar, trans-fats, saturated fat, total fat, or total calories, or increased consumption of fruit, vegetables and wholegrain. Studies were only included if quantitative results were presented by a measure of SEP. Extracted data were categorised with a modified version of the "4Ps" marketing mix, expanded to 6 "Ps": "Price, Place, Product, Prescriptive, Promotion, and Person". RESULTS: Our search identified 31,887 articles. Following screening, 36 studies were included: 18 "Price" interventions, 6 "Place" interventions, 1 "Product" intervention, zero "Prescriptive" interventions, 4 "Promotion" interventions, and 18 "Person" interventions. "Price" interventions were most effective in groups with lower SEP, and may therefore appear likely to reduce inequalities. All interventions that combined taxes and subsidies consistently decreased inequalities. Conversely, interventions categorised as "Person" had a greater impact with increasing SEP, and may therefore appear likely to reduce inequalities. All four dietary counselling interventions appear likely to widen inequalities. We did not find any "Prescriptive" interventions and only one "Product" intervention that presented differential results and had no impact by SEP. More "Place" interventions were identified and none of these interventions were judged as likely to widen inequalities. CONCLUSIONS: Interventions categorised by a "6 Ps" framework show differential effects on healthy eating outcomes by SEP. "Upstream" interventions categorised as "Price" appeared to decrease inequalities, and "downstream" "Person" interventions, especially dietary counselling seemed to increase inequalities. However the vast majority of studies identified did not explore differential effects by SEP. Interventions aimed at improving population health should be routinely evaluated for differential socioeconomic impact.

Quantifying the contribution of statins to the decline in population mean cholesterol by socioeconomic group in England 1991 - 2012: a modelling study.

BACKGROUND: Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statins are effective for cholesterol control in individual patients. At the population level, however, their contribution to total cholesterol decline remains unclear. The aim of this study was to quantify the contribution of statins to the observed fall in population mean cholesterol levels in England over the past two decades, and explore any differences between socioeconomic groups. METHODS AND FINDINGS: This is a modelling study based on data from the Health Survey for England. We analysed changes in observed mean total cholesterol levels in the adult England population between 1991-92 (baseline) and 2011-12. We then compared the observed changes with a counterfactual 'no statins' scenario, where the impact of statins on population total cholesterol was estimated and removed. We estimated uncertainty intervals (UI) using Monte Carlo simulation, where confidence intervals (CI) were impractical. In 2011-12, 13.2% (95% CI: 12.5-14.0%) of the English adult population used statins at least once per week, compared with 1991-92 when the proportion was just 0.5% (95% CI: 0.3-1.0%). Between 1991-92 and 2011-12, mean total cholesterol declined from 5.86 mmol/L (95% CI: 5.82-5.90) to 5.17 mmol/L (95% CI: 5.14-5.20). For 2011-12, mean total cholesterol was lower in more deprived groups. In our 'no statins' scenario we predicted a mean total cholesterol of 5.36 mmol/L (95% CI: 5.33-5.40) for 2011-12. Statins were responsible for approximately 33.7% (95% UI: 28.9-38.8%) of the total cholesterol reduction since 1991-92. The statin contribution to cholesterol reduction was greater among the more deprived groups of women, while showing little socio-economic gradient among men. CONCLUSIONS: Our model suggests that statins explained around a third of the substantial falls in total cholesterol observed in England since 1991. Approximately two thirds of the cholesterol decrease can reasonably be attributed non-pharmacological determinants.

Ascorbic acid, ultraviolet C rays, and glucose but not hyperthermia are elicitors of human ß-defensin 1 mRNA in normal keratinocytes.

Hosts' innate defense systems are upregulated by antimicrobial peptide elicitors (APEs). Our aim was to investigate the effects of hyperthermia, ultraviolet A rays (UVA), and ultraviolet C rays (UVC) as well as glucose and ascorbic acid (AA) on the regulation of human ß-defensin 1 (DEFB1), cathelicidin (CAMP), and interferon-γ (IFNG) genes in normal human keratinocytes (NHK). The indirect in vitro antimicrobial activity against Staphylococcus aureus and Listeria monocytogenes of these potential APEs was tested. We found that AA is a more potent APE for DEFB1 than glucose in NHK. Glucose but not AA is an APE for CAMP. Mild hypo- (35°C) and hyperthermia (39°C) are not APEs in NHK. AA-dependent DEFB1 upregulation below 20 mM predicts in vitro antimicrobial activity as well as glucose- and AA-dependent CAMP and IFNG upregulation. UVC upregulates CAMP and DEFB1 genes but UVA only upregulates the DEFB1 gene. UVC is a previously unrecognized APE in human cells. Our results suggest that glucose upregulates CAMP in an IFN-γ-independent manner. AA is an elicitor of innate immunity that will challenge the current concept of late activation of adaptive immunity of this vitamin. These results could be useful in designing new potential drugs and devices to combat skin infections.

The adenylyl cyclase Rv2212 modifies the proteome and infectivity of Mycobacterium bovis BCG.

All organisms have the capacity to sense and respond to environmental changes. These signals often involve the use of second messengers such as cyclic adenosine monophosphate (cAMP). This second messenger is widely distributed among organisms and coordinates gene expression related with pathogenesis, virulence, and environmental adaptation. Genomic analysis in Mycobacterium tuberculosis has identified 16 adenylyl cyclases (AC) and one phosphodiesterase, which produce and degrade cAMP, respectively. To date, ten AC have been biochemically characterized and only one (Rv0386) has been found to be important during murine infection with M. tuberculosis. Here, we investigated the impact of hsp60-driven Rv2212 gene expression in Mycobacterium bovis Bacillus Calmette-Guerin (BCG) during growth in vitro, and during macrophage and mice infection. We found that hsp60-driven expression of Rv2212 resulted in an increased capacity of replication in murine macrophages but an attenuated phenotype in lungs and spleen when administered intravenously in mice. Furthermore, this strain displayed an altered proteome mainly affecting proteins associated with stress conditions (bfrB, groEL-2, DnaK) that could contribute to the attenuated phenotype observed in mice.

Insecticidal activity and chemical composition of the Morinda lucida essential oil against pulse beetle Callosobruchus maculatus.

Insecticidal activity of essential oil extracted from Morinda lucida was tested on pulse beetle Callosobruchus maculatus, which is a pest that causes serious damage to several pulses. The insecticidal activity was compared with two pesticides, Phostoxin and Primo-ban-20. 120 mixed sex adult C. maculatus were introduced, along with 30 g of cowpeas. Four concentrations (0.40, 0.20, 0.10, and 0.05 µg/mL) of the M. lucida essential oil, Phostoxin, and Primo-ban-20 were tested. Essential oil chemical composition was analyzed by GC-MS. M. lucida essential oil showed a high toxicological effect, producing 100% mortality after 72 hours at a dose of 0.20 µg/mL. M. lucida essential oil had a potent insecticidal activity (LC90 = 0.629 µg/mL) compared to both pesticides, Phostoxin (LC90 = 0.652 µg/mL) and Primo-ban-20 (LC90 = 0.726 µg/mL), at 24 h. The main compounds of the essential oil were the oxygenated monoterpenoids, 1,8-cineole (43.4%), and α-terpinyl acetate (14.5%), and the monoterpene hydrocarbons, mostly sabinene (8.2%) and ß-pinene (4.0%). Results clearly indicate that M. lucida essential oil can be used as an effective alternative for pulse beetle C. maculatus control, and it could be tested against other pulse beetles affecting Asia and Africa and throughout the world, thereby reducing use of synthetic pesticides.

Future declines of coronary heart disease mortality in England and Wales could counter the burden of population ageing.

BACKGROUND: Coronary Heart Disease (CHD) remains a major cause of mortality in the United Kingdom. Yet predictions of future CHD mortality are potentially problematic due to population ageing and increase in obesity and diabetes. Here we explore future projections of CHD mortality in England & Wales under two contrasting future trend assumptions. METHODS: In scenario A, we used the conventional counterfactual scenario that the last-observed CHD mortality rates from 2011 would persist unchanged to 2030. The future number of deaths was calculated by applying those rates to the 2012-2030 population estimates. In scenario B, we assumed that the recent falling trend in CHD mortality rates would continue. Using Lee-Carter and Bayesian Age Period Cohort (BAPC) models, we projected the linear trends up to 2030. We validate our methods using past data to predict mortality from 2002-2011. Then, we computed the error between observed and projected values. RESULTS: In scenario A, assuming that 2011 mortality rates stayed constant by 2030, the number of CHD deaths would increase 62% or approximately 39,600 additional deaths. In scenario B, assuming recent declines continued, the BAPC model (the model with lowest error) suggests the number of deaths will decrease by 56%, representing approximately 36,200 fewer deaths by 2030. CONCLUSIONS: The decline in CHD mortality has been reasonably continuous since 1979, and there is little reason to believe it will soon halt. The commonly used assumption that mortality will remain constant from 2011 therefore appears slightly dubious. By contrast, using the BAPC model and assuming continuing mortality falls offers a more plausible prediction of future trends. Thus, despite population ageing, the number of CHD deaths might halve again between 2011 and 2030. This has implications for how the potential benefits of future cardiovascular strategies might best be calculated and presented.

Evaluation of the inhibition of carbohydrate hydrolyzing enzymes, the antioxidant activity, and the polyphenolic content of Citrus limetta peel extract.

Type 2 diabetes mellitus is one of the most frequent causes of death in Mexico, characterized by chronic hyperglycemia. One alternative strategy for this metabolic abnormality is inhibiting the enzymes responsible for the metabolism of carbohydrates. We evaluated whether the aqueous Citrus limetta peel extract could inhibit the metabolism of carbohydrates. We found that this extract inhibited primarily the enzyme α-amylase by 49.6% at a concentration of 20 mg/mL and to a lesser extent the enzyme α-glucosidase with an inhibition of 28.2% at the same concentration. This inhibition is likely due to the high polyphenol content in the Citrus limetta peel (19.1 mg GAE/g). Antioxidant activity of the Citrus limetta peel demonstrated dose-dependent antioxidant activity, varying from 6.5% at 1.125 mg/mL to 42.5% at 20 mg/mL. The study of these polyphenolic compounds having both antihyperglycemic and antioxidant activities may provide a new approach to the management of type 2 diabetes mellitus.

Assessment of the Appropriateness of Antibiotic Prescriptions in Lesotho Public Hospitals: A Novel Methodology Based on Principles of Antibiotic Prescribing.

The study primarily aimed at assessing the appropriateness of antibiotic prescriptions in a section of public health institutions in Lesotho using an assessment tool formulated from principles of antibiotic prescribing. Relevant data on procedures of infection diagnosis and prescribed antibiotics were collected from both inpatient and outpatient case reports for a one-month period in five public hospitals in Lesotho. These were analyzed for the appropriateness of the prescribed antibiotics. Prescription appropriateness assessment was based on conformities of prescribed antibiotics to criteria developed from pertinent principles of antibiotic prescribing. Assessed prescriptions, 307 inpatient and 865 outpatient prescriptions in total, were classified into categories of appropriateness based on extents to which they satisfied conditions defined by combinations of criteria in the assessment tool. Antibiotic prescriptions from inpatient and outpatient departments of study site hospitals were categorized into groups of different degrees of appropriateness. A total of 32.2% inpatient prescriptions and 78.4% outpatient prescriptions assessed were appropriately written for the empiric treatment of infections for which bacterial pathogens were considered absolute or possible etiologies. The use of prescription assessment tools based on principles of antibiotic prescribing is a feasible option of assessing the appropriateness of antibiotic prescriptions, particularly in low-income countries where expert panels cannot be formed.

The Impact of Appropriate Antibiotic Prescribing on Treatment Evaluation Parameters.

The therapeutic impact of inappropriate prescribing of antibiotics is debatable, particularly in situations where infections are treated empirically with multiply prescribed antibiotics. Prescribers may remain under the illusion that such prescriptions are appropriate on the basis of any observed positive treatment outcomes, even though an antibiotic prescribed in such combination therapy may actually be infective against infecting pathogens. This, inevitably, promotes inappropriate antibiotic prescribing. Prescribers may be motivated to make more conscious attempts to prescribe antibiotics appropriately if it is proven that judicious prescribing of antibiotics has positive impacts on treatment outcomes. The objective of this study was to determine the impact of appropriate prescribing of antibiotics on treatment outcomes, days of patient hospitalization and costs related to antibiotic treatment. Observational data on antibiotic treatment were collected for a one-month period from case notes of all inpatients (n=307) and outpatients (n=865) at five government and mission hospitals in Lesotho. Prescriptions were classified into categories of appropriateness based on extents to which antibiotics were prescribed according to principles. Treatment success rates, mean days of hospitalization and costs of antibiotic treatments of inpatients treated with specified prescription categories were determined. Appropriate prescribing of antibiotics for inpatients had positive impacts on treatment outcomes, patients' days of hospitalization for infections and costs of antibiotic treatments. In outpatient settings, appropriate prescribing of antibiotics failed to show any significant impact on costs of antibiotics. Appropriate prescribing of antibiotics had a positive impact on patients' recovery and costs of antibiotic treatments in inpatient settings.

Transcriptome analysis identifies genes involved in ethanol response of Saccharomyces cerevisiae in Agave tequilana juice.

During ethanol fermentation, yeast cells are exposed to stress due to the accumulation of ethanol, cell growth is altered and the output of the target product is reduced. For Agave beverages, like tequila, no reports have been published on the global gene expression under ethanol stress. In this work, we used microarray analysis to identify Saccharomyces cerevisiae genes involved in the ethanol response. Gene expression of a tequila yeast strain of S. cerevisiae (AR5) was explored by comparing global gene expression with that of laboratory strain S288C, both after ethanol exposure. Additionally, we used two different culture conditions, cells grown in Agave tequilana juice as a natural fermentation media or grown in yeast-extract peptone dextrose as artificial media. Of the 6368 S. cerevisiae genes in the microarray, 657 genes were identified that had different expression responses to ethanol stress due to strain and/or media. A cluster of 28 genes was found over-expressed specifically in the AR5 tequila strain that could be involved in the adaptation to tequila yeast fermentation, 14 of which are unknown such as yor343c, ylr162w, ygr182c, ymr265c, yer053c-a or ydr415c. These could be the most suitable genes for transforming tequila yeast to increase ethanol tolerance in the tequila fermentation process. Other genes involved in response to stress (RFC4, TSA1, MLH1, PAU3, RAD53) or transport (CYB2, TIP20, QCR9) were expressed in the same cluster. Unknown genes could be good candidates for the development of recombinant yeasts with ethanol tolerance for use in industrial tequila fermentation.