1 5224 202 PRIORITIZED RESEARCH FOR THE PREVENTION, TREATMENT, AND REVERSAL OF CHRONIC DISEASE: RECOMMENDATIONS FROM THE LIFESTYLE MEDICINE RESEARCH SUMMIT. DECLINING LIFE EXPECTANCY AND INCREASING ALL-CAUSE MORTALITY IN THE UNITED STATES HAVE BEEN ASSOCIATED WITH UNHEALTHY BEHAVIORS, SOCIOECOLOGICAL FACTORS, AND PREVENTABLE DISEASE. A GROWING BODY OF BASIC SCIENCE, CLINICAL RESEARCH, AND POPULATION HEALTH EVIDENCE POINTS TO THE BENEFITS OF HEALTHY BEHAVIORS, ENVIRONMENTS AND POLICIES TO MAINTAIN HEALTH AND PREVENT, TREAT, AND REVERSE THE ROOT CAUSES OF COMMON CHRONIC DISEASES. SIMILARLY, INNOVATIONS IN RESEARCH METHODOLOGIES, STANDARDS OF EVIDENCE, EMERGENCE OF UNIQUE STUDY COHORTS, AND BREAKTHROUGHS IN DATA ANALYTICS AND MODELING CREATE NEW POSSIBILITIES FOR PRODUCING BIOMEDICAL KNOWLEDGE AND CLINICAL TRANSLATION. TO UNDERSTAND THESE ADVANCES AND INFORM FUTURE DIRECTIONS RESEARCH, THE LIFESTYLE MEDICINE RESEARCH SUMMIT WAS CONVENED AT THE UNIVERSITY OF PITTSBURGH ON DECEMBER 4-5, 2019. THE SUMMIT'S GOAL WAS TO REVIEW CURRENT STATUS AND DEFINE RESEARCH PRIORITIES IN THE SIX CORE AREAS OF LIFESTYLE MEDICINE: PLANT-PREDOMINANT NUTRITION, PHYSICAL ACTIVITY, SLEEP, STRESS, ADDICTIVE BEHAVIORS, AND POSITIVE PSYCHOLOGY/SOCIAL CONNECTION. FORTY INVITED SUBJECT MATTER EXPERTS (1) REVIEWED EXISTING KNOWLEDGE AND GAPS RELATING LIFESTYLE BEHAVIORS TO COMMON CHRONIC DISEASES, SUCH AS CARDIOVASCULAR DISEASE, DIABETES, MANY CANCERS, INFLAMMATORY- AND IMMUNE-RELATED DISORDERS AND OTHER CONDITIONS; AND (2) DISCUSSED THE POTENTIAL FOR APPLYING CUTTING-EDGE MOLECULAR, CELLULAR, EPIGENETIC AND EMERGING SCIENCE KNOWLEDGE AND COMPUTATIONAL METHODOLOGIES, RESEARCH DESIGNS, AND STUDY COHORTS TO ACCELERATE CLINICAL APPLICATIONS ACROSS ALL SIX DOMAINS OF LIFESTYLE MEDICINE. NOTABLY, FEDERAL HEALTH AGENCIES, SUCH AS THE DEPARTMENT OF DEFENSE AND VETERANS ADMINISTRATION HAVE BEGUN TO ADOPT "WHOLE-PERSON HEALTH AND PERFORMANCE" MODELS THAT ADDRESS THESE LIFESTYLE AND ENVIRONMENTAL ROOT CAUSES OF CHRONIC DISEASE AND ASSOCIATED MORBIDITY, MORTALITY, AND COST. RECOMMENDATIONS STRONGLY SUPPORT LEVERAGING EMERGING RESEARCH METHODOLOGIES, SYSTEMS BIOLOGY, AND COMPUTATIONAL MODELING IN ORDER TO ACCELERATE EFFECTIVE CLINICAL AND POPULATION SOLUTIONS TO IMPROVE HEALTH AND REDUCE SOCIETAL COSTS. NEW AND ALTERNATIVE HIERARCHIES OF EVIDENCE ARE ALSO BE NEEDED IN ORDER TO ASSESS THE QUALITY OF EVIDENCE AND DEVELOP EVIDENCE-BASED GUIDELINES ON LIFESTYLE MEDICINE. CHILDREN AND UNDERSERVED POPULATIONS WERE IDENTIFIED AS PRIORITIZED GROUPS TO STUDY. THE COVID-19 PANDEMIC, WHICH DISPROPORTIONATELY IMPACTS PEOPLE WITH CHRONIC DISEASES THAT ARE AMENABLE TO EFFECTIVE LIFESTYLE MEDICINE INTERVENTIONS, MAKES THE SUMMIT'S FINDINGS AND RECOMMENDATIONS FOR FUTURE RESEARCH PARTICULARLY TIMELY AND RELEVANT. 2020 2 1417 39 DIETARY TRENDS AND THE DECLINE IN MALE REPRODUCTIVE HEALTH. OVER THE TWENTIETH CENTURY, MALE REPRODUCTIVE HEALTH HAS SUFFERED A SUBSTANTIAL DECLINE, AS EVIDENCED BY DECREASES IN SPERM COUNTS AND TESTOSTERONE LEVELS AND INCREASES IN REPRODUCTIVE PATHOLOGIES. AT THE SAME TIME, THE PREVALENCE OF CHRONIC DISEASES SUCH AS OBESITY, DIABETES, AND METABOLIC SYNDROME HAS RISEN DRAMATICALLY. METABOLIC AND REPRODUCTIVE HEALTH ARE HIGHLY INTERCONNECTED, SUGGESTING THAT THEIR RESPECTIVE TRENDS ARE INTERTWINED AND, GIVEN THE TIMEFRAME OF SUCH TRENDS, ENVIRONMENTAL AND NOT GENETIC FACTORS ARE MOST LIKELY TO BE THE PRIMARY CAUSES. INDUSTRIALIZATION, WHICH BEGAN IN EUROPE IN THE MID-EIGHTEENTH CENTURY, HAS RESULTED IN PROFOUND CHANGES TO OUR DIET, LIFESTYLE, AND ENVIRONMENT, MANY OF WHICH ARE CAUSAL FACTORS IN THE RISE IN CHRONIC DISEASES. INDUSTRIALIZATION RESULTS IN A NUTRITION TRANSITION FROM AN AGRICULTURAL UNPROCESSED TO A MODERN PROCESSED DIET, INCORPORATING INCREASES IN SUGAR, VEGETABLE OILS, ULTRA-PROCESSED FOODS, LINOLEIC ACID, TRANS-FATS, AND TOTAL ENERGY. THIS DIETARY SHIFT HAS INCURRED NUMEROUS ADVERSE EFFECTS ON METABOLIC AND REPRODUCTIVE HEALTH, CHARACTERIZED BY CHRONIC INFLAMMATION, OXIDATIVE STRESS, AND INSULIN RESISTANCE. MOREOVER, THESE EFFECTS APPEAR TO MULTIPLY ACROSS SUBSEQUENT GENERATIONS VIA EPIGENETIC INHERITANCE. MEN'S FERTILITY IS MARKEDLY AFFECTED BY OBESITY AND DIABETES, WITH AN INCREASE IN TOTAL ENERGY VIA PROCESSED FOOD INTAKE ARGUABLY BEING THE KEY FACTOR DRIVING THE DIABESITY PANDEMIC. IN CONTRAST, WHOLEFOODS RICH IN MICRONUTRIENTS AND PHYTONUTRIENTS SUPPORT MALE FERTILITY AND A HEALTHY BODY WEIGHT. THEREFORE, MEN WANTING TO MAXIMIZE THEIR FERTILITY SHOULD CONSIDER MAKING POSITIVE DIETARY CHANGES, SUCH AS REPLACING PROCESSED FOODS WITH UNPROCESSED FOODS THAT SUPPORT METABOLIC AND REPRODUCTIVE HEALTH. 2023 3 734 52 CANCER HEALTHCARE DISPARITIES AMONG AFRICAN AMERICANS IN THE UNITED STATES. A NEED EXISTS TO EXAMINE RACIAL DISPARITIES IN THE HEALTHCARE ARENA AND THE IMPACT ON PATIENTS WITH CANCER. DESPITE ONGOING EFFORTS TO INCREASE EQUITY IN PRIMARY HEALTHCARE ACCESS, RACIAL AND SOCIOECONOMIC DISPARITIES PERSIST, THUS CONTRIBUTING TO DISPROPORTIONATE TREATMENT OUTCOMES AND SURVIVORSHIP AMONG MINORITY AND LOW-INCOME PATIENTS. SUCH DISPARITIES HAVE BEEN REVEALED IN TREATMENT COHORTS OF PATIENTS WITH MULTIPLE FORMS OF CANCER, INCLUDING BREAST, CERVICAL, OVARIAN, ENDOMETRIAL, PROSTATE, LUNG, COLORECTAL, GASTROINTESTINAL, AND HEPATOCELLULAR, AND HAVE BEEN ATTRIBUTED TO A RANGE OF CO-OCCURRING BEHAVIORAL, SOCIAL DETERMINANTS OF HEALTH, UNDERLYING GENETIC FACTORS, AS WELL AS ACCESS TO EDUCATIONAL OPPORTUNITIES THAT LIMIT THE QUALITY OF INFORMED HEALTHCARE. THESE VARIOUS INTERRELATED FACTORS WIDEN CANCER HEALTHCARE DISPARITIES SYNERGISTICALLY THROUGHOUT UNDERSERVED COMMUNITIES, AND THEIR INFLUENCE HAS BEEN AMPLIFIED BY THE CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC. FUNDAMENTALLY, A LACK OF BASIC AND CLINICAL RESEARCH EXISTS THAT FAILS TO ADEQUATELY REFLECT DIVERSITY AND MINORITY INVOLVEMENT IN DRUG DEVELOPMENT. ALTHOUGH OVERCOMING THE OBSTACLES RESPONSIBLE FOR CHRONIC TREATMENT DISPARITIES IS A FORMIDABLE TASK, PROMISING MEANS OF ACHIEVING MORE UNIFORM QUALITY HEALTHCARE ARE BECOMING MORE CLEARLY ELUCIDATED. TO REDUCE DISEASE PROGRESSION, INCREASE OVERALL SURVIVAL, AND IMPROVE THE HEALTH OF VULNERABLE POPULATIONS, IT IS NECESSARY TO IDENTIFY AND FULLY DISCLOSE ENVIRONMENTAL, BIOLOGICAL, AND ANCESTRAL FACTORS THAT IMPACT THE RISK FOR CANCER; HEAL HISTORICAL FRACTURES WITHIN COMMUNITIES; AND INCREASE PARTICIPATION OF RACIAL AND ETHNIC MINORITIES IN SCREENING EFFORTS AND RESEARCH STUDIES. THIS REQUIRES DEVELOPING A SYSTEM OF JUSTICE AND TRUST BASED ON SPECIFIC, SOLUTION-ORIENTED GRASSROOTS COMMUNITY EFFORTS WORKING IN TANDEM WITH MEDICAL AND PHARMACEUTICAL LEADERS. BY FULLY EXPLORING AND PINPOINTING THE UNDERLYING CAUSES OF HEALTHCARE DISPARITIES, IT SHOULD BE POSSIBLE TO DEFINE STRATEGIES AND INTERVENTIONS MOST LIKELY TO TRANSFORM CANCER CARE. THE ULTIMATE GOAL IS UNDERSTANDING INDIVIDUAL, CULTURAL, AND BIOLOGICAL VULNERABILITIES, INCLUDING ENVIRONMENTAL AND EPIGENETIC LIABILITIES, TO OPTIMIZE CANCER PREVENTION, DIAGNOSIS, AND TREATMENT. 2022 4 805 39 CHALLENGES AND PERSPECTIVES OF THE DOUBLE BURDEN OF MALNUTRITION IN LATIN AMERICA. NUTRITION IS A KEY FACTOR IN THE DEVELOPMENT OF NON-COMMUNICABLE CHRONIC DISEASES (NCCDS), ESPECIALLY CARDIOVASCULAR DISEASES (CVD) AND THEIR RISK FACTORS. THE "DOUBLE BURDEN OF MALNUTRITION" (DBM) IS THE COEXISTENCE OF UNDERNUTRITION AND OVERNUTRITION IN THE SAME POPULATION ACROSS THE LIFE-COURSE. IN LATIN AMERICA, THE TRANSITION FROM A PREDOMINANTLY UNDERWEIGHT TO AN OVERWEIGHT AND OBESE POPULATION HAS INCREASED MORE RAPIDLY THAN IN OTHER REGIONS IN THE WORLD. UNDERNUTRITION AND THE MICRONUTRIENT DEFICIENCIES PARTICULARLY IRON, ZINC, AND VITAMINS A AND D, PRESENT HIGH HETEROGENEITY IN LATIN AMERICAN COUNTRIES, AND ARE CURRENTLY CONSIDERED IMPORTANT PUBLIC HEALTH PROBLEMS. IN THIS REGION, NCCDS ACCOUNT FOR 50% OF THE DISABILITY-ADJUSTED LIFE-YEARS, LED BY CVD. THE MOST PREVALENT CARDIOVASCULAR RISK FACTORS ARE OVERWEIGHT, OBESITY, HYPERTENSION, DYSLIPIDEMIA AND TYPE 2 DIABETES MELLITUS. BECAUSE OF THE COST OF TREATMENT AND THE POTENTIAL YEARS OF LIFE LOST DUE TO PREMATURE DEATH, CVD IS KNOWN TO AFFECT THE POOREST SEGMENTS OF THE POPULATION, AFFECTING COMMUNITIES, AND GOVERNMENTS. MORE THAN 80% OF CVD DEATHS OCCUR IN LOW- AND MIDDLE-INCOME COUNTRIES. THE PERSISTENCE OF DAMAGE IN SOME CELLS DUE TO UNDERNUTRITION MAY EXPLAIN CERTAIN FINDINGS REGARDING THE INCREASE IN NCCD. THESE ASPECTS TOGETHER WITH EPIGENETIC CHANGES HAVE HIGHLIGHTED THE IMPORTANCE OF A LIFELONG APPROACH TO NUTRITIONAL POLICY DEVELOPMENT. REDUCING DBM REQUIRES MAJOR SOCIETAL INTERVENTIONS IN PUBLIC HEALTH AND NUTRITION TO ACHIEVE HOLISTIC CHANGE THAT CAN BE SUSTAINED OVER THE LONG TERM AND SPREAD THROUGHOUT THE GLOBAL FOOD SYSTEM. THE IMPLEMENTATION OF EFFECTIVE STATE POLICIES OF DOUBLE IMPACT ACTIONS SHOULD INFLUENCE BOTH SIDES OF THE BURDEN AND BE CONSIDERED AN URGENT PRIORITY, CONSIDERING COUNTRY-SPECIFIC INEQUALITIES AND SOCIO-DEMOGRAPHIC DIFFERENCES IN THE LATIN AMERICAN REGION, USING DIVERSE AND MULTIDISCIPLINARY STRATEGIES. 2022 5 4080 25 MATERNAL LIFESTYLE INTERVENTIONS: TARGETING PRECONCEPTION HEALTH. ABOUT ONE-THIRD OF WOMEN OF REPRODUCTIVE AGE ARE OBESE, PREDISPOSING BOTH MOTHER AND BABY TO UNFAVOURABLE PREGNANCY OUTCOMES AND INITIATING AN INTERGENERATIONAL CYCLE OF CHRONIC METABOLIC DISORDERS. HERE WE SUMMARISE RECENT RESEARCH ON THE INFLUENCE OF MATERNAL METABOLIC HEALTH ON OFFSPRING SUSCEPTIBILITY TO FUTURE CARDIOMETABOLIC DISEASES. CURRENT PRIMARY LIFESTYLE APPROACHES (I.E., DIET AND EXERCISE INTERVENTIONS) TO HALT THE SUCCESSION OF INHERITED AND EPIGENETIC METABOLIC ABNORMALITIES HAVE MET WITH LIMITED SUCCESS DUE TO LATE IMPLEMENTATION, POOR ADHERENCE, AND/OR GENERIC GUIDELINES. IN OUR OPINION, SUCH INTERVENTIONS MUST COMMENCE PRIOR TO CONCEPTION TO IMPROVE BOTH MATERNAL AND CHILD HEALTH OUTCOMES, WITH NEW APPROACHES URGENTLY NEEDED TO INCREASE ADHERENCE TO PRIMARY LIFESTYLE CHANGES AMONG REPRODUCTIVE-AGE WOMEN. 2020 6 4062 42 MATERNAL AND CHILD HEALTH SERVICES AND AN INTEGRATED, LIFE-CYCLE APPROACH TO THE PREVENTION OF NON-COMMUNICABLE DISEASES. DESCRIBED AS THE 'INVISIBLE EPIDEMIC', NON-COMMUNICABLE DISEASES (NCDS) ARE THE WORLD'S LEADING CAUSE OF DEATH. MOST ARE CAUSED BY PREVENTABLE FACTORS, INCLUDING POOR DIET, TOBACCO USE, HARMFUL USE OF ALCOHOL AND PHYSICAL INACTIVITY. DIABETES, CANCER AND CARDIOVASCULAR AND CHRONIC LUNG DISEASES WERE RESPONSIBLE FOR 38 MILLION (68%) OF GLOBAL DEATHS IN 2012. SINCE 1990, PROPORTIONATE NCD MORTALITY HAS INCREASED SUBSTANTIALLY AS POPULATIONS HAVE AGED AND COMMUNICABLE DISEASES DECLINE. THE MAJORITY OF NCD DEATHS, ESPECIALLY PREMATURE NCD DEATHS (<70 YEARS, 82%), OCCUR IN LOW-INCOME AND MIDDLE-INCOME COUNTRIES, AND AMONG POOR COMMUNITIES WITHIN THEM. ADDRESSING NCDS IS RECOGNISED AS CENTRAL TO THE POST-2015 AGENDA; ACCORDINGLY, NCDS HAVE A SPECIFIC OBJECTIVE AND TARGET IN THE SUSTAINABLE DEVELOPMENT GOALS. WHILE DEATHS FROM NCDS OCCUR MAINLY IN ADULTHOOD, MANY HAVE THEIR ORIGINS IN EARLY LIFE, INCLUDING THROUGH EPIGENETIC MECHANISMS OPERATING BEFORE CONCEPTION. GOOD NUTRITION BEFORE CONCEPTION AND INTERVENTIONS AIMED AT PREVENTING NCDS DURING THE FIRST 1000 DAYS (FROM CONCEPTION TO AGE 2 YEARS), CHILDHOOD AND ADOLESCENCE MAY BE MORE COST-EFFECTIVE THAN MANAGING ESTABLISHED NCDS IN LATER LIFE WITH COSTLY TESTS AND DRUGS. FOLLOWING A LIFE-COURSE APPROACH, MATERNAL AND CHILD HEALTH INTERVENTIONS, BEFORE DELIVERY AND DURING CHILDHOOD AND ADOLESCENCE, CAN PREVENT NCDS AND SHOULD INFLUENCE GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT. THIS PAPER DESCRIBES HOW SUCH AN APPROACH MAY BE PURSUED, INCLUDING THROUGH THE ENGAGEMENT OF NON-HEALTH SECTORS. IT ALSO EMPHASISES EVALUATING AND DOCUMENTING RELATED INITIATIVES TO UNDERWRITE SYSTEMATIC AND EVIDENCE-BASED CROSS-SECTORAL ENGAGEMENT ON NCD PREVENTION IN THE FUTURE. 2017 7 1386 52 DIABETES: AN UPDATE ON THE PANDEMIC AND POTENTIAL SOLUTIONS. DIABETES MELLITUS IS A CHRONIC METABOLIC DISEASE WITH DEADLY, DISABLING, AND COSTLY CONSEQUENCES FOR INDIVIDUALS, FAMILIES, COMMUNITIES, AND COUNTRIES. ALTHOUGH THEY ARE PHENOTYPICALLY DISTINCT, DIABETES SUBTYPES (TYPE 1, TYPE 2, GESTATIONAL, AND OTHER FORMS) ARE ALL DEFINED BY ELEVATED BLOOD GLUCOSE LEVELS. APPROXIMATELY 95 PERCENT OF DIABETES CASES WORLDWIDE ARE TYPE 2 DIABETES (PREVIOUSLY KNOWN AS ADULT-ONSET OR NON-INSULIN-DEPENDENT DIABETES), WHICH IS THE FOCUS OF THIS CHAPTER. TYPE 1 DIABETES (PREVIOUSLY KNOWN AS INSULIN-DEPENDENT DIABETES) MOST COMMONLY BEGINS IN CHILDHOOD AND ADOLESCENCE. GESTATIONAL DIABETES REFERS TO ELEVATED BLOOD GLUCOSE LEVELS DURING PREGNANCY AMONG WOMEN WITHOUT PREVIOUS DIABETES AND IS ASSOCIATED WITH FETAL, BIRTHING, AND EARLY CHILDHOOD COMPLICATIONS AS WELL AS HIGHER RISK OF THE MOTHER DEVELOPING POSTGESTATION DIABETES. THE GROWTH OF DIABETES AND ITS IMPACTS HAVE ACCELERATED WORLDWIDE SINCE THE END OF THE TWENTIETH CENTURY (NCD-RISC 2016), LIKELY CORRELATED WITH EXPANSION OF DIABETES RISK FACTORS, ESPECIALLY POPULATION AGING AND OBESITY. DIABETES IS A MULTIFACTORIAL CONDITION. BECAUSE GENETIC, EPIGENETIC, LIFESTYLE, ECONOMIC, AND PSYCHOSOCIAL FACTORS ALL CONTRIBUTE TO THE DEVELOPMENT OF DIABETES (MCCARTHY 2010; STUMVOLL, GOLDSTEIN, AND VAN HAEFTEN 2005), PREVENTING AND MANAGING THE CONDITION REQUIRE ACTION AT POLICY, PROGRAM, CLINICAL PRACTICE, AND INDIVIDUAL LEVELS (HILL AND OTHERS 2013). RELIABLE AND MEANINGFUL ESTIMATES OF BURDENS, RISK FACTORS, AND EFFECTIVENESS AND COST-EFFECTIVENESS OF INTERVENTIONS AS WELL AS EVALUATIONS OF EXISTING POLICIES, ARE LIMITED; DATA ARE ESPECIALLY SCARCE IN LOW- AND MIDDLE-INCOME COUNTRIES (LMICS). THIS CHAPTER FOCUSES ON WHAT CAN AND SHOULD BE DONE TO ADDRESS DIABETES. WE PRESENT THE AVAILABLE DATA REGARDING GLOBAL BURDENS AND TRENDS IN DIABETES; REVIEW AVAILABLE EVIDENCE AND ASSESS THE EFFECTIVENESS AND COST-EFFECTIVENESS OF INTERVENTIONS TO PREVENT, DETECT, AND CONTROL DIABETES; AND REPORT SUMMARY EXPERT OPINIONS REGARDING THE PRIORITY AND FEASIBILITY OF IMPLEMENTING THESE INTERVENTIONS. ASSIMILATING EVIDENCE FROM COUNTRIES AT DIFFERENT INCOME LEVELS, WE PROVIDE GLOBAL PERSPECTIVES ON THE DIABETES PANDEMIC, RECOMMEND PRIORITY INTERVENTIONS, AND IDENTIFY REMAINING DATA GAPS. 2017 8 2699 34 EXCESS BODY WEIGHT: NOVEL INSIGHTS INTO ITS ROLES IN OBESITY COMORBIDITIES. EXCESS BODY WEIGHT IS A GLOBAL HEALTH PROBLEM DUE TO SEDENTARY LIFESTYLE AND UNHEALTHY DIET, AFFECTING 2 BILLION POPULATION WORLDWIDE. OBESITY IS A MAJOR RISK FACTOR FOR METABOLIC DISEASES. NOTABLY, THE METABOLIC RISK OF OBESITY LARGELY DEPENDS ON BODY WEIGHT DISTRIBUTION, OF WHICH VISCERAL ADIPOSE TISSUES BUT NOT SUBCUTANEOUS FATS ARE CLOSELY ASSOCIATED WITH OBESITY COMORBIDITIES, INCLUDING TYPE 2 DIABETES, NON-ALCOHOLIC FATTY LIVER DISEASE, CARDIOVASCULAR DISEASE AND CERTAIN TYPES OF CANCER. LATEST MULTI-OMICS AND MECHANISTICAL STUDIES REPORTED THE CRUCIAL INVOLVEMENT OF GENETIC AND EPIGENETIC ALTERATIONS, ADIPOKINES DYSREGULATION, IMMUNITY CHANGES, IMBALANCE OF WHITE AND BROWN ADIPOSE TISSUES, AND GUT MICROBIAL DYSBIOSIS IN MEDIATING THE PATHOGENIC ASSOCIATION BETWEEN VISCERAL ADIPOSE TISSUES AND COMORBIDITIES. IN THIS REVIEW, WE EXPLORE THE EPIDEMIOLOGY OF EXCESS BODY WEIGHT AND THE UP-TO-DATE MECHANISM OF HOW EXCESS BODY WEIGHT AND OBESITY LEAD TO CHRONIC COMPLICATIONS. WE ALSO EXAMINE THE UTILIZATION OF VISCERAL FAT MEASUREMENT AS AN ACCURATE CLINICAL PARAMETER FOR RISK ASSESSMENT IN HEALTHY INDIVIDUALS AND CLINICAL OUTCOME PREDICTION IN OBESE SUBJECTS. IN ADDITION, CURRENT APPROACHES FOR THE PREVENTION AND TREATMENT OF EXCESS BODY WEIGHT AND ITS RELATED METABOLIC COMORBIDITIES ARE FURTHER DISCUSSED. 2023 9 2801 29 FEMALE OBESITY: SHORT- AND LONG-TERM CONSEQUENCES ON THE OFFSPRING. THE WORLDWIDE PREVALENCE OF OBESITY HAS RISEN OVER THE PAST FEW DECADES AND WOMEN ARE CURRENTLY MORE LIKELY THAN EVER TO ENTER PREGNANCY OBESE. PRE-PREGNANCY OBESITY AND EXCESSIVE GESTATIONAL WEIGHT GAIN INCREASE MISCARRIAGE RATES AND OBSTETRIC AND NEONATAL COMPLICATIONS, WHICH RESULT IN A LOWER HEALTHY LIVE BIRTH RATE. IN ADDITION TO ITS NEGATIVE CONSEQUENCES FOR THE MOTHER, OBESITY HAS BEEN SHOWN TO BE AN IMPORTANT RISK FACTOR FOR CHRONIC ILLNESSES, SUCH AS CARDIOVASCULAR DISEASE, METABOLIC SYNDROME AND TYPE 2 DIABETES IN THE ADOLESCENCE AND ADULTHOOD OF THE OFFSPRING. MOREOVER, MATERNAL OBESITY CAUSES PSYCHOLOGICAL PROBLEMS, PHYSICAL DISABILITIES AND HIGHER HEALTHCARE COSTS. FETAL PROGRAMMING OF METABOLIC FUNCTION INDUCED BY OBESITY, THROUGH PHYSIOLOGICAL AND/OR EPIGENETIC MECHANISMS, MAY HAVE AN INTERGENERATIONAL EFFECT AND COULD, THUS, PERPETUATE OBESITY IN THE NEXT GENERATION. IN ORDER TO BREAK THIS VICIOUS CIRCLE AND AVOID SERIOUS SHORT- AND LONG-TERM NEGATIVE OUTCOMES FOR BOTH MOTHERS AND FETUSES, THE PREVENTION AND ADEQUATE MANAGEMENT OF OBESITY AND GESTATIONAL WEIGHT GAIN ARE ESSENTIAL. 2013 10 6860 41 [OBESITY EPIDEMIC: CURRENT EVIDENCE, CHALLENGES AND FUTURE DIRECTIONS]. THE OBESITY EPIDEMIC IS A PHENOMENON THAT HAS BEEN WIDELY STUDIED IN RECENT DECADES BUT IS STILL INCOMPLETELY UNDERSTOOD, AND ITS CONTROL IS FAR FROM THE DESIRABLE LEVEL IN VIEW OF THE INCREASING PREVALENCE FIGURES OBSERVED WORLDWIDE. THIS PAPER CONDUCTS A NARRATIVE REVIEW WITH THE AIM OF PROVIDING UPDATED EVIDENCE ON THE GLOBAL OBESITY EPIDEMIC, AND PARTICULARLY ON THE SITUATION IN LATIN AMERICA AND ARGENTINA, IDENTIFYING THE MAIN CHALLENGES AND FUTURE DIRECTIONS FOR ADDRESSING THIS PUBLIC HEALTH PROBLEM. IT FIRST DESCRIBES THE CURRENT BURDEN AND INCREASING TRENDS IN THE PREVALENCE OF OBESITY, IN THE OVERALL POPULATION AND BY POPULATION GROUPS, AND ITS POSSIBLE ASSOCIATION WITH GENETIC AND EPIGENETIC ASPECTS. IT ALSO SUMMARIZES THE DIRECT AND INDIRECT SOCIOECONOMIC CONSEQUENCES OF THIS EPIDEMIC, AS WELL AS RECENT STRATEGIES AND INITIATIVES FOCUSED ON OBESITY PREVENTION, WITH SPECIAL ATTENTION TO THOSE REPORTED AS THE MOST EFFICIENT IN THE LATIN AMERICAN CONTEXT. THIS REVIEW IDENTIFIED SOME PENDING CHALLENGES IN THE REGION, THE INTEGRATED APPROACH TO THE DOUBLE BURDEN OF MALNUTRITION AND THE GROWING CHILDHOOD OVERWEIGHT; AND IT POINTS OUT SOME EMERGING APPROACHES, SUCH AS THE SYNDEMIC APPROACH, AS POTENTIALLY USEFUL TO UNDERSTAND AND ADDRESS THIS COMPLEX PROBLEM IN THE CURRENT CONTEXT. IN CONCLUSION, IT HIGHLIGHTS THE IMPORTANCE OF IMPLEMENTING RENEWED, MORE EFFICIENT AND EVIDENCE-BASED STRATEGIES TO CONTROL THE GROWING PREVALENCE OF OBESITY, WHICH WOULD ALSO IMPACT ON THE BURDEN OF RELATED CHRONIC DISEASES, AND THUS ON THE ECONOMY AND WELL-BEING OF LATIN AMERICAN SOCIETIES. 2023 11 2584 36 EPIGENETICS OF OBESITY. OBESITY IS A METABOLIC DISEASE, WHICH IS BECOMING AN EPIDEMIC HEALTH PROBLEM: IT HAS BEEN RECENTLY DEFINED IN TERMS OF GLOBAL PANDEMIC. OVER THE YEARS, THE APPROACHES THROUGH FAMILY, TWINS AND ADOPTION STUDIES LED TO THE IDENTIFICATION OF SOME CAUSAL GENES IN MONOGENIC FORMS OF OBESITY BUT THE ORIGINS OF THE PANDEMIC OF OBESITY CANNOT BE CONSIDERED ESSENTIALLY DUE TO GENETIC FACTORS, BECAUSE HUMAN GENOME IS NOT LIKELY TO CHANGE IN JUST A FEW YEARS. EPIGENETIC STUDIES HAVE OFFERED IN RECENT YEARS VALUABLE TOOLS FOR THE UNDERSTANDING OF THE WORLDWIDE SPREAD OF THE PANDEMIC OF OBESITY. THE INVOLVEMENT OF EPIGENETIC MODIFICATIONS-DNA METHYLATION, HISTONE TAILS, AND MIRNAS MODIFICATIONS-IN THE DEVELOPMENT OF OBESITY IS MORE AND MORE EVIDENT. IN THE EPIGENETIC LITERATURE, THERE ARE EVIDENCES THAT THE ENTIRE EMBRYO-FETAL AND PERINATAL PERIOD OF DEVELOPMENT PLAYS A KEY ROLE IN THE PROGRAMMING OF ALL HUMAN ORGANS AND TISSUES. THEREFORE, THE MOLECULAR MECHANISMS INVOLVED IN THE EPIGENETIC PROGRAMMING REQUIRE A NEW AND GENERAL PATHOGENIC PARADIGM, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE THEORY, TO EXPLAIN THE CURRENT EPIDEMIOLOGICAL TRANSITION, THAT IS, THE WORLDWIDE INCREASE OF CHRONIC, DEGENERATIVE, AND INFLAMMATORY DISEASES SUCH AS OBESITY, DIABETES, CARDIOVASCULAR DISEASES, NEURODEGENERATIVE DISEASES, AND CANCER. OBESITY AND ITS RELATED COMPLICATIONS ARE MORE AND MORE ASSOCIATED WITH ENVIRONMENTAL POLLUTANTS (OBESOGENS), GUT MICROBIOTA MODIFICATIONS AND UNBALANCED FOOD INTAKE, WHICH CAN INDUCE, THROUGH EPIGENETIC MECHANISMS, WEIGHT GAIN, AND ALTERED METABOLIC CONSEQUENCES. 2016 12 30 42 A BRIEF LOOK AT HASHIMOTO'S DISEASE, ADRENAL INCIDENTALOMAS, OBESITY AND INSULIN RESISTANCE-COULD ENDOCRINE DISRUPTORS BE THE OTHER SIDE OF THE SAME COIN? HASHIMOTO'S DISEASE (HD) IS THE MOST COMMON CAUSE OF HYPOTHYROIDISM IN DEVELOPED COUNTRIES. THE EXACT PATHOMECHANISM BEHIND IT HAS NOT BEEN CLEARLY ESTABLISHED; HOWEVER, AN INTERPLAY OF GENETIC SUSCEPTIBILITY, ENVIRONMENTAL TRIGGERS (INCLUDING DIET) AND EPIGENETIC FACTORS SEEMS TO BE INVOLVED. AMONG THE LATTER, INCREASINGLY MORE ATTENTION HAS BEEN PAID TO SOME HORMONALLY ACTIVE SUBSTANCES, KNOWN AS ENDOCRINE DISRUPTORS, WHICH ARE COMMONLY USED WORLDWIDE. HD HAS BECOME A CONDITION WIDELY REPORTED IN THE MEDIA, ACTING AS A CULPRIT FOR INEXPLICABLE WEIGHT GAIN, CHRONIC FATIGUE OR WEAKNESS. NEVERTHELESS, THE RECOGNITION OF HD IS UNDENIABLY INCREASING AND REPRESENTS A MAJOR PUBLIC HEALTH BURDEN. AT THE SAME TIME, IMPROVING ACCESS TO IMAGING TESTS HAS INCREASED THE NUMBER OF INCIDENTALLY DIAGNOSED ADRENAL TUMORS. ABOVE ALL, THE WIDESPREAD USE OF CHEST COMPUTED TOMOGRAPHY (CT) DUE TO THE COVID-19 PANDEMIC HAS CONTRIBUTED TO FREQUENT INCIDENTAL DETECTION OF ADRENAL LESIONS. FORTUNATELY, A VAST MAJORITY OF THESE FINDINGS ARE ASYMPTOMATIC BENIGN TUMORS WITH NO EXCESSIVE HORMONAL ACTIVITY, AND THEREFORE, THEY ARE DEFINED AS ADRENAL INCIDENTALOMAS (AIS). INTERESTINGLY, RECENT STUDIES HAVE INDICATED THAT PATIENTS WITH AIS ARE MORE PRONE TO OBESITY AND INSULIN RESISTANCE. ALTHOUGH MUTUAL RELATIONSHIPS BETWEEN THE THYROID AND THE ADRENAL GLANDS HAVE BEEN STUDIED WIDELY, STILL, LITTLE IS KNOWN ABOUT THE POSSIBLE PATHOPHYSIOLOGICAL ASSOCIATIONS BETWEEN THYROID AUTOIMMUNITY AND THE OCCURRENCE OF ADRENAL INCIDENTALOMAS. THIS ARTICLE PRESENTS A BRIEF REVIEW OF THE COMMON ENDOCRINE DISORDERS WITH A SPECIAL FOCUS ON THE FREQUENTLY COEXISTING INSULIN RESISTANCE AND/OR OBESITY. FURTHERMORE, IN RESPONSE TO THE RECENT GROWING INTEREST IN ENDOCRINE DISRUPTORS, WITH THEIR TRANSGENERATIONAL EPIGENETIC EFFECTS THAT INFLUENCE HORMONAL SYSTEM FUNCTION, A CONCISE OVERVIEW OF THE TOPIC HAS ALSO BEEN INCLUDED. 2023 13 1398 43 DIET, GUT MICROBIOME AND EPIGENETICS: EMERGING LINKS WITH INFLAMMATORY BOWEL DISEASES AND PROSPECTS FOR MANAGEMENT AND PREVENTION. INFLAMMATORY BOWEL DISEASES (IBD) REPRESENT A GROWING PUBLIC HEALTH CONCERN DUE TO INCREASING INCIDENCE WORLDWIDE. THE CURRENT NOTION ON THE PATHOGENESIS OF IBD IS THAT GENETICALLY SUSCEPTIBLE INDIVIDUALS DEVELOP INTOLERANCE TO DYSREGULATED GUT MICROFLORA (DYSBIOSIS) AND CHRONIC INFLAMMATION DEVELOPS AS A RESULT OF ENVIRONMENTAL TRIGGERS. AMONG THE ENVIRONMENTAL FACTORS ASSOCIATED WITH IBD, DIET PLAYS AN IMPORTANT ROLE IN MODULATING THE GUT MICROBIOME, INFLUENCING EPIGENETIC CHANGES, AND, THEREFORE, COULD BE APPLIED AS A THERAPEUTIC TOOL TO IMPROVE THE DISEASE COURSE. NEVERTHELESS, THE CURRENT DIETARY RECOMMENDATIONS FOR DISEASE PREVENTION AND MANAGEMENT ARE SCARCE AND HAVE WEAK EVIDENCE. THIS REVIEW SUMMARISES THE CURRENT KNOWLEDGE ON THE COMPLEX INTERACTIONS BETWEEN DIET, MICROBIOME AND EPIGENETICS IN IBD. WHEREAS AN OVERABUNDANCE OF CALORIES AND SOME MACRONUTRIENTS INCREASE GUT INFLAMMATION, SEVERAL MICRONUTRIENTS HAVE THE POTENTIAL TO MODULATE IT. IMMUNONUTRITION HAS EMERGED AS A NEW CONCEPT PUTTING FORWARD THE IMPORTANCE OF VITAMINS SUCH AS VITAMINS A, C, E, AND D, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS SUCH AS ZINC, SELENIUM, MANGANESE AND IRON. HOWEVER, WHEN ASSESSED IN CLINICAL TRIALS, SPECIFIC MICRONUTRIENTS EXERTED A LIMITED BENEFIT. BEYOND NUTRIENTS, AN ANTI-INFLAMMATORY DIETARY PATTERN AS A COMPLEX INTERVENTION APPROACH HAS BECOME POPULAR IN RECENT YEARS. HENCE, EXCLUSIVE ENTERAL NUTRITION IN PAEDIATRIC CROHN'S DISEASE IS THE ONLY NUTRITIONAL INTERVENTION CURRENTLY RECOMMENDED AS A FIRST-LINE THERAPY. OTHER NUTRITIONAL INTERVENTIONS OR SPECIFIC DIETS INCLUDING THE SPECIFIC CARBOHYDRATE DIET (SCD), THE LOW FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES, AND POLYOL (FODMAP) DIET AND, MOST RECENTLY, THE MEDITERRANEAN DIET HAVE SHOWN STRONG ANTI-INFLAMMATORY PROPERTIES AND SHOW PROMISE FOR IMPROVING DISEASE SYMPTOMS. MORE WORK IS REQUIRED TO EVALUATE THE ROLE OF INDIVIDUAL FOOD COMPOUNDS AND COMPLEX NUTRITIONAL INTERVENTIONS WITH THE POTENTIAL TO DECREASE INFLAMMATION AS A MEANS OF PREVENTION AND MANAGEMENT OF IBD. 2017 14 6732 26 WESTERN DIET AND THE IMMUNE SYSTEM: AN INFLAMMATORY CONNECTION. THE CONSUMPTION OF WESTERN-TYPE CALORICALLY RICH DIETS COMBINED WITH CHRONIC OVERNUTRITION AND A SEDENTARY LIFESTYLE IN WESTERN SOCIETIES EVOKES A STATE OF CHRONIC METABOLIC INFLAMMATION, TERMED METAFLAMMATION. METAFLAMMATION CONTRIBUTES TO THE DEVELOPMENT OF MANY PREVALENT NON-COMMUNICABLE DISEASES (NCDS), AND THESE LIFESTYLE-ASSOCIATED PATHOLOGIES REPRESENT A RISING PUBLIC HEALTH PROBLEM WITH GLOBAL EPIDEMIC DIMENSIONS. A BETTER UNDERSTANDING OF HOW MODERN LIFESTYLE AND WESTERN DIET (WD) ACTIVATE IMMUNE CELLS IS ESSENTIAL FOR THE DEVELOPMENT OF EFFICIENT PREVENTIVE AND THERAPEUTIC STRATEGIES FOR COMMON NCDS. HERE, WE REVIEW THE CURRENT MECHANISTIC UNDERSTANDING OF HOW THE WESTERN LIFESTYLE CAN INDUCE METAFLAMMATION, AND WE DISCUSS HOW THIS KNOWLEDGE CAN BE TRANSLATED TO PROTECT THE PUBLIC FROM THE HEALTH BURDEN ASSOCIATED WITH THEIR SELECTED LIFESTYLE. 2019 15 2881 36 FUTURE PERSPECTIVES OF PERSONALIZED WEIGHT LOSS INTERVENTIONS BASED ON NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA. AS OBESITY HAS BECOME A MAJOR GLOBAL PUBLIC HEALTH CHALLENGE, A LARGE NUMBER OF STUDIES HAVE ANALYZED DIFFERENT STRATEGIES AIMED AT INDUCING A NEGATIVE ENERGY BALANCE AND, CONSEQUENTLY, BODY WEIGHT LOSS. HOWEVER, MOST EXISTING WEIGHT LOSS PROGRAMS ARE GENERALLY UNSUCCESSFUL, SO SEVERAL INTERVENTIONS HAVE BEEN CARRIED OUT TO IDENTIFY PHYSIOLOGIC AND BEHAVIORAL FACTORS CONCERNING THIS VARIABILITY IN ORDER TO IMPLEMENT MORE PERSONALIZED TREATMENT. NOWADAYS, AN INDIVIDUALIZED APPROACH IS BEING PROPOSED THROUGH SO-CALLED PERSONALIZED NUTRITION, WHEREBY NOT ONLY THE PHENOTYPE BUT ALSO THE GENOTYPE IS USED FOR CUSTOMIZED NUTRITION TREATMENT. REGARDING BODY WEIGHT REGULATION, APPROXIMATELY 70 POLYMORPHISMS HAVE BEEN IDENTIFIED IN OR NEAR GENES RELATED TO ENERGY EXPENDITURE, APPETITE, ADIPOGENESIS, INSULIN RESISTANCE, AND LIPID METABOLISM. ALTHOUGH PERSONALIZED NUTRITION REFERS MAINLY TO GENETIC MAKEUP, RECENT ADVANCES IN THE INVESTIGATION OF THE EPIGENOME AND THE MICROBIOME OPEN THE DOOR TO IMPLEMENT MORE PERSONALIZED RECOMMENDATIONS FOR BODY WEIGHT MANAGEMENT. IN THIS CONTEXT, RECENT STUDIES HAVE DEMONSTRATED THE EXISTENCE OF SEVERAL EPIGENETIC MARKERS THAT MAY MODIFY GENE EXPRESSION AND COULD BE INVOLVED IN THE OUTCOME OF WEIGHT LOSS INTERVENTIONS. MOREOVER, DIFFERENT STUDIES HAVE SHOWN THAT DIETARY INTERVENTIONS COULD AFFECT THE COMPOSITION OF GUT MICROBIOTA AND HAVE AN IMPACT ON BODY WEIGHT. THE INTEGRATION OF NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA MAY LEAD TO THE DESIGN OF MORE PERSONALIZED DIETARY TREATMENTS TO PREVENT CHRONIC DISEASES AND TO OPTIMIZE THE INDIVIDUAL'S RESPONSE TO DIETARY INTERVENTIONS. 2015 16 65 26 A JOURNEY FROM MICROENVIRONMENT TO MACROENVIRONMENT: THE ROLE OF METAFLAMMATION AND EPIGENETIC CHANGES IN CARDIORENAL DISEASE. CHRONIC NON-COMMUNICABLE DISEASES HAVE BECOME A PANDEMIC PUBLIC PROBLEM IN THE 21ST CENTURY, CAUSING ENORMOUS BURDEN ON THE ECONOMY, HEALTH AND QUALITY OF LIFE OF SOCIETIES. THE ROLE OF A CHRONIC INFLAMMATORY STATE IN THE PATHOGENESIS OF CHRONIC DISEASE HAS BEEN MORE COMPREHENSIVELY RECOGNIZED BY RECENT FINDINGS. THE NEW PARADIGM 'METAFLAMMATION' FOCUSES ON METABOLISM-INDUCED (HIGH FAT OR FRUCTOSE-BASED DIET OR EXCESSIVE CALORIE INTAKE) CHRONIC INFLAMMATION. THERE IS A CLOSE CORRELATION BETWEEN THE INCREASED INCIDENCE OF CHRONIC KIDNEY DISEASE (CKD) AND CHRONIC HEART FAILURE WITH BOTH INCREASED INFLAMMATORY MARKER LEVELS AND WESTERN-TYPE DIET. IN THIS REVIEW WE DESCRIBE THE CONCEPT OF METAFLAMMATION, ITS ROLE IN THE DEVELOPMENT OF CKD AND CHRONIC HEART DISEASE, THE MOLECULAR AND SIGNALLING PATHWAYS INVOLVED AND THE THERAPEUTIC CONSEQUENCES. 2019 17 1098 39 COLLATERAL DAMAGE: MATERNAL OBESITY DURING PREGNANCY CONTINUES TO RISE. IMPORTANCE: THE PANDEMIC OF OBESITY DURING PREGNANCY NOW AFFLICTS 1 OUT OF EVERY 2 PREGNANT WOMEN IN THE UNITED STATES. EVEN THOUGH UNINTENDED PREGNANCY HAS DECREASED TO 45% OF ALL PREGNANCIES, 50% OF THOSE UNINTENDED PREGNANCIES OCCUR IN OBESE WOMEN. OBJECTIVE: THIS STUDY AIMS TO IDENTIFY WHY CURRENT LIFESTYLE INTERVENTIONS FOR OBESE PREGNANCY ARE NOT EFFECTIVE AND WHAT THE NEWER COMPLICATIONS ARE FOR OBESITY DURING PREGNANCY. EVIDENCE ACQUISITION: AVAILABLE LITERATURES ON CURRENT TREATMENTS FOR MATERNAL OBESITY WERE REVIEWED FOR EFFECTIVENESS. EMERGING MATERNAL AND INFANT COMPLICATIONS FROM OBESITY DURING PREGNANCY WERE EXAMINED FOR SIGNIFICANCE. RESULTS: LIMITATIONS IN SUCCESSFUL INTERVENTIONS FELL INTO 3 BASIC CATEGORIES TO INCLUDE THE FOLLOWING: (1) PRECONCEPTION WEIGHT LOSS; (2) BARIATRIC SURGERY BEFORE PREGNANCY; AND (3) PREVENTION OF EXCESSIVE GESTATIONAL WEIGHT GAIN DURING PREGNANCY. EMERGING SIGNIFICANT PHYSIOLOGICAL CHANGES FROM MATERNAL OBESITY IS COMPOSED OF INFLAMMATION (PLACENTA AND HUMAN MILK), METABOLISM (HORMONES, MICROBIOME, FATTY ACIDS), AND OFFSPRING OUTCOMES (BODY COMPOSITION, CONGENITAL MALFORMATIONS, CHRONIC KIDNEY DISEASE, ASTHMA, NEURODEVELOPMENT, AND BEHAVIOR). CONCLUSIONS AND RELEVANCE: ARE CURRENT PREPREGNANCY LIFESTYLE AND BEHAVIORAL INTERVENTIONS FEASIBLE TO PREVENT MATERNAL OBESITY COMPLICATIONS? EPIGENETIC AND METABOLOMIC RESEARCH WILL BE CRITICAL TO DETERMINE WHAT IS NEEDED TO BLUNT THE EFFECTS OF MATERNAL OBESITY AND TO DISCOVER SUCCESSFUL TREATMENT. 2020 18 3408 37 HOW WESTERN DIET AND LIFESTYLE DRIVE THE PANDEMIC OF OBESITY AND CIVILIZATION DISEASES. WESTERNIZED POPULATIONS ARE PLAGUED BY A PLETHORA OF CHRONIC NON-INFECTIOUS DEGENERATIVE DISEASES, TERMED AS "CIVILIZATION DISEASES", LIKE OBESITY, DIABETES, CARDIOVASCULAR DISEASES, CANCER, AUTOIMMUNE DISEASES, ALZHEIMER'S DISEASE AND MANY MORE, DISEASES WHICH ARE RARE OR VIRTUALLY ABSENT IN HUNTER-GATHERERS AND OTHER NON-WESTERNIZED POPULATIONS. THERE IS A GROWING AWARENESS THAT THE CAUSE OF THIS AMAZING DISCREPANCY LIES IN THE PROFOUND CHANGES IN DIET AND LIFESTYLE DURING RECENT HUMAN HISTORY. THIS PAPER SHOWS THAT THE TRANSITION FROM PALEOLITHIC NUTRITION TO WESTERN DIETS, ALONG WITH LACK OF CORRESPONDING GENETIC ADAPTATIONS, CAUSE SIGNIFICANT DISTORTIONS OF THE FINE-TUNED METABOLISM THAT HAS EVOLVED OVER MILLIONS OF YEARS OF HUMAN EVOLUTION IN ADAPTATION TO PALEOLITHIC DIETS. WITH THE INCREASING SPREAD OF WESTERN DIET AND LIFESTYLE WORLDWIDE, OVERWEIGHT AND CIVILIZATION DISEASES ARE ALSO RAPIDLY INCREASING IN DEVELOPING COUNTRIES. IT IS SUGGESTED THAT THE DIET-RELATED KEY CHANGES IN THE DEVELOPMENTAL PROCESS INCLUDE AN INCREASED PRODUCTION OF REACTIVE OXYGEN SPECIES AND OXIDATIVE STRESS, DEVELOPMENT OF HYPERINSULINEMIA AND INSULIN RESISTANCE, LOW-GRADE INFLAMMATION AND AN ABNORMAL ACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM AND THE RENIN-ANGIOTENSIN SYSTEM, ALL OF WHICH PLAY PIVOTAL ROLES IN THE DEVELOPMENT OF DISEASES OF CIVILIZATION. IN ADDITION, DIET-RELATED EPIGENETIC CHANGES AND FETAL PROGRAMMING PLAY AN IMPORTANT ROLE. THE SUGGESTED PATHOMECHANISM IS ALSO ABLE TO EXPLAIN THE WELL-KNOWN BUT NOT COMPLETELY UNDERSTOOD CLOSE RELATIONSHIP BETWEEN OBESITY AND THE WIDE RANGE OF COMORBIDITIES, LIKE TYPE 2 DIABETES MELLITUS, CARDIOVASCULAR DISEASE, ETC., AS DISEASES OF THE SAME ETIOPATHOLOGY. CHANGING OUR LIFESTYLE IN ACCORDANCE WITH OUR GENETIC MAKEUP, INCLUDING DIET AND PHYSICAL ACTIVITY, MAY HELP PREVENT OR LIMIT THE DEVELOPMENT OF THESE DISEASES. 2019 19 4807 41 OBESITY IN LOW- AND MIDDLE-INCOME COUNTRIES: BURDEN, DRIVERS, AND EMERGING CHALLENGES. WE HAVE REVIEWED THE DISTINCTIVE FEATURES OF EXCESS WEIGHT, ITS CAUSES, AND RELATED PREVENTION AND MANAGEMENT EFFORTS, AS WELL AS DATA GAPS AND RECOMMENDATIONS FOR FUTURE RESEARCH IN LOW- AND MIDDLE-INCOME COUNTRIES (LMICS). OBESITY IS RISING IN EVERY REGION OF THE WORLD, AND NO COUNTRY HAS BEEN SUCCESSFUL AT REVERSING THE EPIDEMIC ONCE IT HAS BEGUN. IN LMICS, OVERWEIGHT IS HIGHER IN WOMEN COMPARED WITH MEN, IN URBAN COMPARED WITH RURAL SETTINGS, AND IN OLDER COMPARED WITH YOUNGER INDIVIDUALS; HOWEVER, THE URBAN-RURAL OVERWEIGHT DIFFERENTIAL IS SHRINKING IN MANY COUNTRIES. OVERWEIGHT OCCURS ALONGSIDE PERSISTENT BURDENS OF UNDERWEIGHT IN LMICS, ESPECIALLY IN YOUNG WOMEN. CHANGES IN THE GLOBAL DIET AND PHYSICAL ACTIVITY ARE AMONG THE HYPOTHESIZED LEADING CONTRIBUTORS TO OBESITY. EMERGING RISK FACTORS INCLUDE ENVIRONMENTAL CONTAMINANTS, CHRONIC PSYCHOSOCIAL STRESS, NEUROENDOCRINE DYSREGULATION, AND GENETIC/EPIGENETIC MECHANISMS. DATA ON EFFECTIVE STRATEGIES TO PREVENT THE ONSET OF OBESITY IN LMICS OR ELSEWHERE ARE LIMITED. EXPANDING THE RESEARCH IN THIS AREA IS A KEY PRIORITY AND HAS IMPORTANT POSSIBILITIES FOR REVERSE INNOVATION THAT MAY ALSO INFORM INTERVENTIONS IN HIGH-INCOME COUNTRIES. 2017 20 264 39 ADVANCING ASTHMA CARE: THE GLASS IS ONLY HALF FULL! OVER THE PAST 20 YEARS, THERE HAS BEEN A CONCERTED EFFORT IN THE UNITED STATES TO REDUCE MORBIDITY RELATED TO CHRONIC DISEASE, INCLUDING ASTHMA. ATTENTION WAS INITIALLY DIRECTED TOWARD ASTHMA IN RESPONSE TO THE RECOGNITION THAT ASTHMA MORTALITY WAS INCREASING AND THAT THE BURDEN OF DISEASE WAS SIGNIFICANT. THESE EFFORTS TO ADDRESS ASTHMA MORTALITY LED TO MANY NEW INITIATIVES TO DEVELOP CLINICAL PRACTICE GUIDELINES, IMPLEMENT THE ASTHMA GUIDELINES INTO CLINICAL PRACTICE, CONDUCT RESEARCH TO FILL THE GAPS IN THE GUIDELINES, AND CONTINUOUSLY REVISE THE ASTHMA GUIDELINES AS MORE INFORMATION BECAME AVAILABLE. AN ASSESSMENT OF OUR PROGRESS SHOWS SIGNIFICANT ACCOMPLISHMENTS IN RELATION TO REDUCING ASTHMA MORTALITY AND HOSPITALIZATIONS. CONSEQUENTLY, WE ARE NOW AT A CROSSROADS IN ASTHMA CARE. ALTHOUGH WE HAVE RECOGNIZED SOME REMARKABLE ACCOMPLISHMENTS IN REDUCING ASTHMA MORTALITY AND MORBIDITY, THE AVAILABILITY OF NEW TOOLS TO MONITOR DISEASE ACTIVITY, INCLUDING BIOMARKERS AND EPIGENETIC MARKERS, ALONG WITH INFORMATION TECHNOLOGY SYSTEMS TO MONITOR ASTHMA CONTROL HOLD SOME PROMISE IN IDENTIFYING GAPS IN DISEASE MANAGEMENT. THESE ADVANCES SHOULD PROMPT THE EVOLUTION OF NEW STRATEGIES AND NEW TREATMENTS TO FURTHER REDUCE DISEASE BURDEN. IT NOW BECOMES IMPERATIVE TO CONTINUE A FOCUS ON WAYS TO FURTHER REDUCE THE BURDEN OF ASTHMA AND PREVENT ITS ONSET. 2011