1 4062 162 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 2 6743 53 WHITHER THE ETIOPATHOGENESIS (AND SCOLIOGENY) OF ADOLESCENT IDIOPATHIC SCOLIOSIS? INCORPORATING PRESENTATIONS ON SCOLIOGENY AT THE 2012 IRSSD AND SRS MEETINGS. THIS PAPER AIMS TO INTEGRATE INTO CURRENT UNDERSTANDING OF AIS CAUSATION, ETIOPATHOGENETIC INFORMATION PRESENTED AT TWO MEETINGS DURING 2012 NAMELY, THE INTERNATIONAL RESEARCH SOCIETY OF SPINAL DEFORMITIES (IRSSD) AND THE SCOLIOSIS RESEARCH SOCIETY (SRS). THE ULTIMATE HOPE IS TO PREVENT THE OCCURRENCE OR PROGRESSION OF THE SPINAL DEFORMITY OF AIS WITH NON-INVASIVE TREATMENT, POSSIBLY MEDICAL. THIS MIGHT BE ATTAINED BY PERSONALISED POLYMECHANISTIC PREVENTIVE THERAPY TARGETING THE APPROPRIATE ETIOLOGY AND/OR ETIOPATHOGENETIC PATHWAYS, TO AVOID FUSION AND MAINTAIN SPINAL MOBILITY. ALTHOUGH CONSIDERABLE PROGRESS HAD BEEN MADE IN THE PAST TWO DECADES IN UNDERSTANDING THE ETIOPATHOGENESIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), IT STILL LACKS AN AGREED THEORY OF ETIOPATHOGENESIS. ONE PROBLEM MAY BE THAT AIS RESULTS NOT FROM ONE CAUSE, BUT SEVERAL THAT INTERACT WITH VARIOUS GENETIC PREDISPOSING FACTORS. THERE IS A VIEW THERE ARE TWO OTHER PATHOGENIC PROCESSES FOR IDIOPATHIC SCOLIOSIS NAMELY, INITIATING (OR INDUCING), AND THOSE THAT CAUSE CURVE PROGRESSION. TWIN STUDIES AND OBSERVATIONS OF FAMILY AGGREGATION HAVE REVEALED SIGNIFICANT GENETIC CONTRIBUTIONS TO IDIOPATHIC SCOLIOSIS, THAT PLACE AIS AMONG OTHER COMMON DISEASE OR COMPLEX TRAITS WITH A HIGH HERITABILITY INTERPRETED BY THE GENETIC VARIANT HYPOTHESIS OF DISEASE. WE SUMMARIZE ETIOPATHOGENETIC KNOWLEDGE OF AIS AS THEORIES OF PATHOGENESIS INCLUDING RECENT MULTIPLE CONCEPTS, AND BLOOD TESTS FOR AIS BASED ON PREDICTIVE BIOMARKERS AND GENETIC VARIANTS THAT SIGNIFY DISEASE RISK. THERE IS INCREASING EVIDENCE FOR THE POSSIBILITY OF AN UNDERLYING NEUROLOGICAL DISORDER FOR AIS, RESEARCH WHICH HOLDS PROMISE. LIKE BRAIN RESEARCH, MOST AIS WORKERS FOCUS ON THEIR OWN CORNER AND THERE IS A NEED FOR GREATER INTEGRATION OF RESEARCH EFFORT. EPIGENETICS, A RELATIVELY RECENT FIELD, EVALUATES FACTORS CONCERNED WITH GENE EXPRESSION IN RELATION TO ENVIRONMENT, DISEASE, NORMAL DEVELOPMENT AND AGING, WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. RESEARCH ON THE ROLE OF ENVIRONMENTAL FACTORS, EPIGENETICS AND CHRONIC NON-COMMUNICABLE DISEASES (NCDS) INCLUDING ADIPOSITY, AFTER A SLOW START, HAS EXPLODED IN THE LAST DECADE. NOT SO FOR AIS RESEARCH AND THE ENVIRONMENT WHERE, EXCEPT FOR MONOZYGOTIC TWIN STUDIES, THERE ARE ONLY SPORADIC REPORTS TO SUGGEST THAT ENVIRONMENTAL FACTORS ARE AT WORK IN ETIOLOGY. HERE, WE EXAMINE EPIGENETIC CONCEPTS AS THEY MAY RELATE TO HUMAN DEVELOPMENT, NORMAL LIFE HISTORY PHASES AND AIS PATHOGENESIS. ALTHOUGH AIS IS NOT REGARDED AS AN NCD, LIKE THEM, IT IS ASSOCIATED WITH WHOLE ORGANISM METABOLIC PHENOMENA, INCLUDING LOWER BODY MASS INDEX, LOWER CIRCULATING LEPTIN LEVELS AND OTHER SYSTEMIC DISORDERS. SOME EPIGENETIC RESEARCH APPLIED TO SILVER-RUSSELL SYNDROME AND ADIPOSITY IS EXAMINED, FROM WHICH SUGGESTIONS ARE MADE FOR CONSIDERATION OF AIS EPIGENETIC RESEARCH, CROSS-SECTIONAL AND LONGITUDINAL. THE WORD SCOLIOGENY IS SUGGESTED TO INCLUDE ETIOLOGY, PATHOGENESIS AND PATHOMECHANISM. 2013 3 6742 48 WHITHER THE ETIOPATHOGENESIS (AND SCOLIOGENY) OF ADOLESCENT IDIOPATHIC SCOLIOSIS? ALTHOUGH CONSIDERABLE PROGRESS HAD BEEN MADE IN THE PAST TWO DECADES IN UNDERSTANDING THE ETIOPATHOGENESIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), IT STILL LACKS AN AGREED THEORY OF ETIOPATHOGENESIS. ONE PROBLEM MAY BE THAT AIS RESULTS NOT FROM ONE CAUSE, BUT SEVERAL THAT INTERACT WITH VARIOUS GENETIC PREDISPOSING FACTORS. THERE IS A VIEW THERE ARE TWO OTHER PATHOGENIC PROCESSES FOR IDIOPATHIC SCOLIOSIS NAMELY, INITIATING (OR INDUCING), AND THOSE THAT CAUSE CURVE PROGRESSION. TWIN STUDIES AND OBSERVATIONS OF FAMILY AGGREGATION HAVE REVEALED SIGNIFICANT GENETIC CONTRIBUTIONS TO IDIOPATHIC SCOLIOSIS, THAT PLACE AIS AMONG OTHER COMMON DISEASE OR COMPLEX TRAITS WITH A HIGH HERITABILITY INTERPRETED BY THE GENETIC VARIANT HYPOTHESIS OF DISEASE. WE SUMMARIZE ETIOPATHOGENETIC KNOWLEDGE OF AIS AS THEORIES OF PATHOGENESIS INCLUDING RECENT MULTIPLE CONCEPTS, AND BLOOD TESTS FOR AIS BASED ON PREDICTIVE BIOMARKERS AND GENETIC VARIANTS THAT SIGNIFY DISEASE RISK. THERE IS INCREASING EVIDENCE FOR THE POSSIBILITY OF AN UNDERLYING NEUROLOGICAL DISORDER FOR AIS, RESEARCH WHICH HOLDS PROMISE. LIKE BRAIN RESEARCH, MOST AIS WORKERS FOCUS ON THEIR OWN CORNER AND THERE IS A NEED FOR GREATER INTEGRATION OF RESEARCH EFFORT. EPIGENETICS, A RELATIVELY RECENT FIELD, EVALUATES FACTORS CONCERNED WITH GENE EXPRESSION IN RELATION TO ENVIRONMENT, DISEASE, NORMAL DEVELOPMENT AND AGING, WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. RESEARCH ON THE ROLE OF ENVIRONMENTAL FACTORS, EPIGENETICS AND CHRONIC NON-COMMUNICABLE DISEASES (NCDS) INCLUDING ADIPOSITY, AFTER A SLOW START, HAS EXPLODED IN THE LAST DECADE. NOT SO FOR AIS RESEARCH AND THE ENVIRONMENT WHERE, EXCEPT FOR MONOZYGOTIC TWIN STUDIES, THERE ARE ONLY SPORADIC REPORTS TO SUGGEST THAT ENVIRONMENTAL FACTORS ARE AT WORK IN ETIOLOGY. HERE, WE EXAMINE EPIGENETIC CONCEPTS AS THEY MAY RELATE TO HUMAN DEVELOPMENT, NORMAL LIFE HISTORY PHASES AND AIS PATHOGENESIS. ALTHOUGH AIS IS NOT REGARDED AS AN NCD, LIKE THEM, IT IS ASSOCIATED WITH WHOLE ORGANISM METABOLIC PHENOMENA, INCLUDING LOWER BODY MASS INDEX, LOWER CIRCULATING LEPTIN LEVELS AND OTHER SYSTEMIC DISORDERS. SOME EPIGENETIC RESEARCH APPLIED TO SILVER-RUSSELL SYNDROME AND ADIPOSITY IS EXAMINED, FROM WHICH SUGGESTIONS ARE MADE FOR CONSIDERATION OF AIS EPIGENETIC RESEARCH, CROSS-SECTIONAL AND LONGITUDINAL. THE WORD SCOLIOGENY IS SUGGESTED TO INCLUDE ETIOLOGY, PATHOGENESIS AND PATHOMECHANISM. 2012 4 1374 39 DEVELOPMENTAL PROGRAMMING OF ADULT DISEASE: REPROGRAMMING BY MELATONIN? ADULT-ONSET CHRONIC NON-COMMUNICABLE DISEASES (NCDS) CAN ORIGINATE FROM EARLY LIFE THROUGH SO-CALLED THE "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD) OR "DEVELOPMENTAL PROGRAMMING". THE DOHAD CONCEPT OFFERS THE "REPROGRAMMING" STRATEGY TO SHIFT THE TREATMENT FROM ADULTHOOD TO EARLY LIFE, BEFORE CLINICAL DISEASE IS APPARENT. MELATONIN, AN ENDOGENOUS INDOLEAMINE PRODUCED BY THE PINEAL GLAND, HAS PLEIOTROPIC BIOACTIVITIES THOSE ARE BENEFICIAL IN A VARIETY OF HUMAN DISEASES. EMERGING EVIDENCE SUPPORT THAT MELATONIN IS CLOSELY INTER-RELATED TO OTHER PROPOSED MECHANISMS CONTRIBUTING TO THE DEVELOPMENTAL PROGRAMMING OF A VARIETY OF CHRONIC NCDS. RECENT ANIMAL STUDIES HAVE BEGUN TO UNRAVEL THE MULTIFUNCTIONAL ROLES OF MELATONIN IN MANY EXPERIMENTAL MODELS OF DEVELOPMENTAL PROGRAMMING. EVEN THOUGH SOME PROGRESS HAS BEEN MADE IN RESEARCH ON MELATONIN AS A REPROGRAMMING STRATEGY TO PREVENT DOHAD-RELATED NCDS, FUTURE HUMAN STUDIES SHOULD AIM AT FILLING THE TRANSLATIONAL GAP BETWEEN ANIMAL MODELS AND CLINICAL TRIALS. HERE, WE REVIEW SEVERAL KEY THEMES ON THE REPROGRAMMING EFFECTS OF MELATONIN IN DOHAD RESEARCH. WE HAVE PARTICULARLY FOCUSED ON THE FOLLOWING AREAS: MECHANISMS OF DEVELOPMENTAL PROGRAMMING; THE INTERRELATIONSHIP BETWEEN MELATONIN AND MECHANISMS UNDERLYING DEVELOPMENTAL PROGRAMMING; PATHOPHYSIOLOGICAL ROLES OF MELATONIN IN PREGNANCY AND FETAL DEVELOPMENT; AND INSIGHT PROVIDED BY ANIMAL MODELS TO SUPPORT MELATONIN AS A REPROGRAMMING THERAPY. RATES OF NCDS ARE INCREASING FASTER THAN ANTICIPATED ALL OVER THE WORLD. HENCE, THERE IS AN URGENT NEED TO UNDERSTAND REPROGRAMMING MECHANISMS OF MELATONIN AND TO TRANSLATE EXPERIMENTAL RESEARCH INTO CLINICAL PRACTICE FOR HALTING A GROWING LIST OF DOHAD-RELATED NCDS. 2017 5 244 38 ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), ENVIRONMENT, EXPOSOME AND EPIGENETICS: A MOLECULAR PERSPECTIVE OF POSTNATAL NORMAL SPINAL GROWTH AND THE ETIOPATHOGENESIS OF AIS WITH CONSIDERATION OF A NETWORK APPROACH AND POSSIBLE IMPLICATIONS FOR MEDICAL THERAPY. GENETIC FACTORS ARE BELIEVED TO PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS). DISCORDANT FINDINGS FOR MONOZYGOTIC (MZ) TWINS WITH AIS SHOW THAT ENVIRONMENTAL FACTORS INCLUDING DIFFERENT INTRAUTERINE ENVIRONMENTS ARE IMPORTANT IN ETIOLOGY, BUT WHAT THESE ENVIRONMENTAL FACTORS MAY BE IS UNKNOWN. RECENT EVIDENCE FOR COMMON CHRONIC NON-COMMUNICABLE DISEASES SUGGESTS EPIGENETIC DIFFERENCES MAY UNDERLIE MZ TWIN DISCORDANCE, AND BE THE LINK BETWEEN ENVIRONMENTAL FACTORS AND PHENOTYPIC DIFFERENCES. DNA METHYLATION IS ONE IMPORTANT EPIGENETIC MECHANISM OPERATING AT THE INTERFACE BETWEEN GENOME AND ENVIRONMENT TO REGULATE PHENOTYPIC PLASTICITY WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. THE WORD EXPOSOME REFERS TO THE TOTALITY OF ENVIRONMENTAL EXPOSURES FROM CONCEPTION ONWARDS, COMPRISING FACTORS IN EXTERNAL AND INTERNAL ENVIRONMENTS. THE WORD EXPOSOME IS USED HERE ALSO IN RELATION TO PHYSIOLOGIC AND ETIOPATHOGENETIC FACTORS THAT AFFECT NORMAL SPINAL GROWTH AND MAY INDUCE THE DEFORMITY OF AIS. IN NORMAL POSTNATAL SPINAL GROWTH WE PROPOSE A NEW TERM AND CONCEPT, PHYSIOLOGIC GROWTH-PLATE EXPOSOME FOR THE NORMAL PROCESSES PARTICULARLY OF THE INTERNAL ENVIRONMENTS THAT MAY HAVE EPIGENETIC EFFECTS ON GROWTH PLATES OF VERTEBRAE. IN AIS, WE PROPOSE A NEW TERM AND CONCEPT PATHOPHYSIOLOGIC SCOLIOGENIC EXPOSOME FOR THE ABNORMAL PROCESSES IN MOLECULAR PATHWAYS PARTICULARLY OF THE INTERNAL ENVIRONMENT CURRENTLY EXPRESSED AS ETIOPATHOGENETIC HYPOTHESES; THESE ARE SUGGESTED TO HAVE DEFORMING EFFECTS ON THE GROWTH PLATES OF VERTEBRAE AT CELL, TISSUE, STRUCTURE AND/OR ORGAN LEVELS THAT ARE CONSIDERED TO BE EPIGENETIC. NEW RESEARCH IS REQUIRED FOR CHROMATIN MODIFICATIONS INCLUDING DNA METHYLATION IN AIS SUBJECTS AND VERTEBRAL GROWTH PLATES EXCISED AT SURGERY. IN ADDITION, CONSIDERATION IS NEEDED FOR A POSSIBLE NETWORK APPROACH TO ETIOPATHOGENESIS BY CONSTRUCTING AIS DISEASOMES. THESE APPROACHES MAY LEAD THROUGH SCREENING, GENETIC, EPIGENETIC, BIOCHEMICAL, METABOLIC PHENOTYPES AND PHARMACOGENOMIC RESEARCH TO IDENTIFY SUSCEPTIBLE INDIVIDUALS AT RISK AND MODULATE ABNORMAL MOLECULAR PATHWAYS OF AIS. THE POTENTIAL OF EPIGENETIC-BASED MEDICAL THERAPY FOR AIS CANNOT BE ASSESSED AT PRESENT, AND MUST AWAIT NEW RESEARCH DERIVED FROM THE EVALUATION OF EPIGENETIC CONCEPTS OF SPINAL GROWTH IN HEALTH AND DEFORMITY. THE TENETS OUTLINED HERE FOR AIS ARE APPLICABLE TO OTHER MUSCULOSKELETAL GROWTH DISORDERS INCLUDING INFANTILE AND JUVENILE IDIOPATHIC SCOLIOSIS. 2011 6 6732 28 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 7 4007 43 LOW BIRTHWEIGHT AS A RISK FACTOR FOR NON-COMMUNICABLE DISEASES IN ADULTS. ACCORDING TO STUDIES UNDERTAKEN OVER THE PAST 40 YEARS, LOW BIRTHWEIGHT (LBW) IS NOT ONLY A SIGNIFICANT PREDICTOR OF PERINATAL DEATH AND MORBIDITY, BUT ALSO INCREASES THE RISK OF CHRONIC NON-COMMUNICABLE DISEASES (NCDS) IN ADULTHOOD. THE PURPOSE OF THIS PAPER IS TO SUMMARIZE THE RESEARCH ON LBW AS A RISK FACTOR FOR NCDS IN ADULTS. THE BARKER HYPOTHESIS WAS BASED ON THE FINDING THAT ADULTS WITH AN LBW OR AN UNHEALTHY INTRAUTERINE ENVIRONMENT, AS WELL AS A RAPID CATCH-UP, DIE DUE TO NCDS. OVER THE LAST FEW DECADES, TERMINOLOGY SUCH AS THRIFTY GENES, FETAL PROGRAMMING, DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD), AND EPIGENETIC FACTORS HAVE BEEN COINED. THE MOST COMMON NCDS INCLUDE CARDIOVASCULAR DISEASE, DIABETES MELLITUS TYPE 2 (DMT2), HYPERTENSION (HT), DYSLIPIDEMIA, PROTEINURIA, AND CHRONIC KIDNEY DISEASE (CKD). STUDIES IN MOTHERS WHO EXPERIENCED FAMINE AND THOSE THAT SOLELY REPORTED BIRTH WEIGHT AS A RISK FACTOR FOR MORTALITY SUPPORT THE CONCEPT. ALTHOUGH THE ETIOLOGY OF NCD IS UNKNOWN, BARRY BRENNER EXPLAINED THE NOTION OF A LOW GLOMERULAR NUMBER (NGLOM) IN LBW CHILDREN, FOLLOWED BY THE PROGRESSION TO HYPERFILTRATION AS THE PHYSIOPATHOLOGIC ETIOLOGY OF HT AND CKD IN ADULTS BASED ON GUYTON'S RENAL PHYSIOLOGY WORK. AUTOPSIES OF SEVERAL ETHNIC GROUPS HAVE REVEALED ANATOMOPATHOLOGIC EVIDENCE IN FETUSES AND ADULT KIDNEYS. BECAUSE OF THE RENAL RESERVE, DEMONSTRATING RENAL FUNCTION IN PROPORTION TO RENAL VOLUME IN VIVO IS MORE DIFFICULT IN ADULTS. THE GREATEST IMPACT OF THESE THEORIES CAN BE SEEN IN PEDIATRICS AND OBSTETRICS PRACTICE. 2021 8 5619 43 SCALING UP PRENATAL NUTRITION COULD REDUCE THE GLOBAL BURDEN OF NONCOMMUNICABLE DISEASES IN THE NEXT GENERATION: A MODELING ANALYSIS. BACKGROUND: NUTRITIONAL CONDITIONS DURING PREGNANCY MAY INFLUENCE THE EPIGENETIC DEVELOPMENT OF AN INDIVIDUAL AND CONSEQUENTLY THEIR LATER-LIFE RISK OF NONCOMMUNICABLE DISEASE (NCD). IMPROVING NUTRITION FOR PREGNANT FEMALES MAY THEREFORE SERVE THE DUAL PURPOSE OF DIRECTLY IMPROVING PREGNANCY OUTCOMES AND PREVENTING NCDS IN THE NEXT GENERATION. OBJECTIVES: WE ESTIMATED THE IMPACT OF PRENATAL SUPPLEMENTATION WITH IRON AND FOLIC ACID (IFA), MULTIPLE MICRONUTRIENTS (MMS), OR CALCIUM AT 50%, 75%, OR 90% COVERAGE ON FUTURE NCDS BY AGE AND SEX IN 2015. METHODS: WE USED SECONDARY DATA SOURCES FROM 132 COUNTRIES TO QUANTIFY THE CASES OF DIABETES AND HYPERTENSION AND THE DEATHS FROM SELECTED NCDS THAT COULD BE AVERTED OR DELAYED BY SCALING UP PRENATAL MICRONUTRIENT SUPPLEMENTATION. RESULTS: GLOBALLY, >51,000 NCD DEATHS, 6 MILLION CASES OF HYPERTENSION, AND 3 MILLION CASES OF DIABETES COULD BE PREVENTED PER OFFSPRING BIRTH COHORT IF MOTHERS WERE PRENATALLY SUPPLEMENTED WITH MMS AT 90% COVERAGE. FOR IFA THESE NUMBERS WOULD BE ROUGHLY HALF. CALCIUM SUPPLEMENTATION AT 90% COULD DELAY 51,000 DEATHS PER BIRTH COHORT. OUR MODEL SUGGESTS THAT SUBSTANTIAL NUMBERS OF NCD DEATHS AND CASES OF HYPERTENSION AND DIABETES COULD BE PREVENTED IN FUTURE GENERATIONS BY SCALING UP MICRONUTRIENT SUPPLEMENTATION FOR MOTHERS DURING PREGNANCY. CONCLUSIONS: HIGHLIGHTING THE ADDITIONAL BENEFITS OF PROVEN NUTRITION INTERVENTIONS IS CRITICAL IN ENSURING ADEQUATE AND SUSTAINED INVESTMENTS, AND PROGRAMMATIC INTEGRATION. AS THE DOUBLE BURDEN OF DISEASE CONTINUES TO GROW, POPULATION-WIDE EFFORTS TO SCALE UP MICRONUTRIENT SUPPLEMENTATION TO PREGNANT FEMALES COULD HELP PREVENT BOTH UNDERNUTRITION AND CHRONIC DISEASE. 2022 9 2226 40 EPIGENETIC MODIFICATIONS INDUCED BY NUTRIENTS IN EARLY LIFE PHASES: GENDER DIFFERENCES IN METABOLIC ALTERATION IN ADULTHOOD. METABOLIC CHRONIC DISEASES, ALSO NAMED NONCOMMUNICABLE DISEASES (NCDS), ARE CONSIDERED MULTIFACTORIAL PATHOLOGIES, WHICH ARE DRAMATICALLY INCREASED DURING THE LAST DECADES. NONCOMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASES, OBESITY, DIABETES MELLITUS, CANCERS, AND CHRONIC RESPIRATORY DISEASES MARKEDLY INCREASE MORBIDITY, MORTALITY, AND SOCIOECONOMIC COSTS. MOREOVER, NCDS INDUCE SEVERAL AND COMPLEX CLINICAL MANIFESTATIONS THAT LEAD TO A GRADUAL DETERIORATION OF HEALTH STATUS AND QUALITY OF LIFE OF AFFECTED INDIVIDUALS. MULTIPLE FACTORS ARE INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF THESE DISEASES SUCH AS SEDENTARY BEHAVIOR, SMOKING, POLLUTION, AND UNHEALTHY DIET. INDEED, NUTRITION HAS A PIVOTAL ROLE IN MAINTAINING HEALTH, AND DIETARY IMBALANCES REPRESENT MAJOR DETERMINANTS FAVORING CHRONIC DISEASES THROUGH METABOLIC HOMEOSTASIS ALTERATIONS. IN PARTICULAR, IT APPEARS THAT SPECIFIC NUTRIENTS AND ADEQUATE NUTRITION ARE IMPORTANT IN ALL PERIODS OF LIFE, BUT THEY ARE ESSENTIAL DURING SPECIFIC TIMES IN EARLY LIFE SUCH AS PRENATAL AND POSTNATAL PHASES. INDEED, EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES REPORT THE DELETERIOUS EFFECTS OF AN INCORRECT NUTRITION ON HEALTH STATUS SEVERAL DECADES LATER IN LIFE. DURING THE LAST DECADE, A GROWING INTEREST ON THE POSSIBLE ROLE OF EPIGENETIC MECHANISMS AS LINK BETWEEN NUTRITIONAL IMBALANCES AND NCDS DEVELOPMENT HAS BEEN OBSERVED. FINALLY, BECAUSE OF THE PIVOTAL ROLE OF THE HORMONES IN FAT, CARBOHYDRATE, AND PROTEIN METABOLISM REGULATION THROUGHOUT LIFE, IT IS EXPECTED THAT ANY HORMONAL MODIFICATION OF THESE PROCESSES CAN IMBALANCE METABOLISM AND FAT STORAGE. THEREFORE, A PARTICULAR INTEREST TO SEVERAL CHEMICALS ABLE TO ACT AS ENDOCRINE DISRUPTORS HAS BEEN RECENTLY DEVELOPED. IN THIS REVIEW, WE WILL PROVIDE AN OVERVIEW AND DISCUSS THE EPIGENETIC ROLE OF SOME SPECIFIC NUTRIENTS AND CHEMICALS IN THE MODULATION OF PHYSIOLOGICAL AND PATHOLOGICAL MECHANISMS. 2019 10 1415 32 DIETARY POLYPHENOLS AND THEIR RELATIONSHIP TO THE MODULATION OF NON-COMMUNICABLE CHRONIC DISEASES AND EPIGENETIC MECHANISMS: A MINI-REVIEW. CHRONIC NON-COMMUNICABLE DISEASES (NCDS) HAVE BEEN CONSIDERED A GLOBAL HEALTH PROBLEM, CHARACTERIZED AS DISEASES OF MULTIPLE FACTORS, WHICH ARE DEVELOPED THROUGHOUT LIFE, AND REGARDLESS OF GENETICS AS A RISK FACTOR OF IMPORTANT RELEVANCE, THE INCREASE IN MORTALITY ATTRIBUTED TO THE DISEASE TO ENVIRONMENTAL FACTORS AND THE LIFESTYLE ONE LEADS. ALTHOUGH THE REACTIVE SPECIES (ROS/RNS) ARE NECESSARY FOR SEVERAL PHYSIOLOGICAL PROCESSES, THEIR OVERPRODUCTION IS DIRECTLY RELATED TO THE PATHOGENESIS AND AGGRAVATION OF NCDS. IN CONTRAST, DIETARY POLYPHENOLS HAVE BEEN WIDELY ASSOCIATED WITH MINIMIZING OXIDATIVE STRESS AND INFLAMMATION. IN ADDITION TO THEIR ANTIOXIDANT POWER, POLYPHENOLS HAVE ALSO DRAWN ATTENTION FOR BEING ABLE TO MODULATE BOTH GENE EXPRESSION AND MODIFY EPIGENETIC ALTERATIONS, SUGGESTING AN ESSENTIAL INVOLVEMENT IN THE PREVENTION AND/OR DEVELOPMENT OF SOME PATHOLOGIES. THEREFORE, THIS REVIEW BRIEFLY EXPLAINED THE MECHANISMS IN THE DEVELOPMENT OF SOME NCDS, FOLLOWED BY A SUMMARY OF SOME EVIDENCE RELATED TO THE INTERACTION OF POLYPHENOLS IN OXIDATIVE STRESS, AS WELL AS THE MODULATION OF EPIGENETIC MECHANISMS INVOLVED IN THE MANAGEMENT OF NCDS. 2023 11 1738 45 EARLY DEVELOPMENTAL CONDITIONING OF LATER HEALTH AND DISEASE: PHYSIOLOGY OR PATHOPHYSIOLOGY? EXTENSIVE EXPERIMENTAL ANIMAL STUDIES AND EPIDEMIOLOGICAL OBSERVATIONS HAVE SHOWN THAT ENVIRONMENTAL INFLUENCES DURING EARLY DEVELOPMENT AFFECT THE RISK OF LATER PATHOPHYSIOLOGICAL PROCESSES ASSOCIATED WITH CHRONIC, ESPECIALLY NONCOMMUNICABLE, DISEASE (NCD). THIS FIELD IS RECOGNIZED AS THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD). WE DISCUSS THE EXTENT TO WHICH DOHAD REPRESENTS THE RESULT OF THE PHYSIOLOGICAL PROCESSES OF DEVELOPMENTAL PLASTICITY, WHICH MAY HAVE POTENTIAL ADVERSE CONSEQUENCES IN TERMS OF NCD RISK LATER, OR WHETHER IT IS THE MANIFESTATION OF PATHOPHYSIOLOGICAL PROCESSES ACTING IN EARLY LIFE BUT ONLY BECOMING APPARENT AS DISEASE LATER. WE ARGUE THAT THE EVIDENCE SUGGESTS THE FORMER, THROUGH THE OPERATION OF CONDITIONING PROCESSES INDUCED ACROSS THE NORMAL RANGE OF DEVELOPMENTAL ENVIRONMENTS, AND WE SUMMARIZE CURRENT KNOWLEDGE OF THE PHYSIOLOGICAL PROCESSES INVOLVED. THE ADAPTIVE PATHWAY TO LATER RISK ACCORDS WITH CURRENT CONCEPTS IN EVOLUTIONARY DEVELOPMENTAL BIOLOGY, ESPECIALLY THOSE CONCERNING PARENTAL EFFECTS. OUTSIDE THE NORMAL RANGE, EFFECTS ON DEVELOPMENT CAN RESULT IN NONADAPTIVE PROCESSES, AND WE REVIEW THEIR UNDERLYING MECHANISMS AND CONSEQUENCES. NEW CONCEPTS CONCERNING THE UNDERLYING EPIGENETIC AND OTHER MECHANISMS INVOLVED IN BOTH DISRUPTIVE AND NONDISRUPTIVE PATHWAYS TO DISEASE ARE REVIEWED, INCLUDING THE EVIDENCE FOR TRANSGENERATIONAL PASSAGE OF RISK FROM BOTH MATERNAL AND PATERNAL LINES. THESE CONCEPTS HAVE WIDER IMPLICATIONS FOR UNDERSTANDING THE CAUSES AND POSSIBLE PREVENTION OF NCDS SUCH AS TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE, FOR BROADER SOCIAL POLICY AND FOR THE INCREASING ATTENTION PAID IN PUBLIC HEALTH TO THE LIFECOURSE APPROACH TO NCD PREVENTION. 2014 12 1932 36 ENVIRONMENTAL EXPOSURES: AN UNDERRECOGNIZED CONTRIBUTION TO NONCOMMUNICABLE DISEASES. PREVIOUS ATTEMPTS TO DETERMINE THE DEGREE TO WHICH EXPOSURE TO ENVIRONMENTAL FACTORS CONTRIBUTE TO NONCOMMUNICABLE DISEASES (NCDS) HAVE BEEN VERY CONSERVATIVE AND HAVE SIGNIFICANTLY UNDERESTIMATED THE ACTUAL CONTRIBUTION OF THE ENVIRONMENT FOR AT LEAST TWO REASONS. FIRSTLY, MOST PREVIOUS REPORTS HAVE EXCLUDED THE CONTRIBUTION OF LIFESTYLE BEHAVIORAL RISK FACTORS, BUT THESE USUALLY INVOLVE SIGNIFICANT EXPOSURE TO ENVIRONMENTAL CHEMICALS THAT INCREASE RISK OF DISEASE. SECONDLY, EARLY LIFE EXPOSURE TO CHEMICAL CONTAMINANTS IS NOW CLEARLY ASSOCIATED WITH AN ELEVATED RISK OF SEVERAL DISEASES LATER IN LIFE, BUT THESE CONNECTIONS ARE OFTEN DIFFICULT TO DISCERN. THIS IS ESPECIALLY TRUE FOR ASTHMA AND NEURODEVELOPMENTAL CONDITIONS, BUT THERE IS ALSO A MAJOR CONTRIBUTION TO THE DEVELOPMENT OF OBESITY AND CHRONIC DISEASES. MOST CANCERS ARE CAUSED BY ENVIRONMENTAL EXPOSURES IN GENETICALLY SUSCEPTIBLE INDIVIDUALS. IN ADDITION, NEW INFORMATION SHOWS SIGNIFICANT ASSOCIATIONS BETWEEN CARDIOVASCULAR DISEASES AND DIABETES AND EXPOSURE TO ENVIRONMENTAL CHEMICALS PRESENT IN AIR, FOOD, AND WATER. THESE RELATIONSHIPS LIKELY REFLECT THE COMBINATION OF EPIGENETIC EFFECTS AND GENE INDUCTION. ENVIRONMENTAL FACTORS CONTRIBUTE SIGNIFICANTLY MORE TO NCDS THAN PREVIOUS REPORTS HAVE SUGGESTED. PREVENTION NEEDS TO SHIFT FOCUS FROM INDIVIDUAL RESPONSIBILITY TO SOCIETAL RESPONSIBILITY AND AN UNDERSTANDING THAT EFFECTIVE PREVENTION OF NCDS ULTIMATELY RELIES ON IMPROVED ENVIRONMENTAL MANAGEMENT TO REDUCE EXPOSURE TO MODIFIABLE RISKS. 2013 13 4419 32 MOLECULAR AND EPIGENETIC MARKERS AS PROMISING TOOLS TO QUANTIFY THE EFFECT OF OCCUPATIONAL EXPOSURES AND THE RISK OF DEVELOPING NON-COMMUNICABLE DISEASES. NON-COMMUNICABLE DISEASES (NCDS) ARE CHRONIC DISEASES THAT ARE BY FAR THE LEADING CAUSE OF DEATH IN THE WORLD. MANY OCCUPATIONAL HAZARDS, TOGETHER WITH SOCIAL, ECONOMIC AND DEMOGRAPHIC FACTORS, HAVE BEEN ASSOCIATED TO NCDS DEVELOPMENT. GENETIC SUSCEPTIBILITY OR ENVIRONMENTAL EXPOSURES ALONE ARE NOT USUALLY SUFFICIENT TO EXPLAIN THE PATHOGENESIS OF NCDS, BUT CAN BE INTEGRATED IN A MORE COMPLEX SCENARIO THAT CAN RESULT IN PATHOLOGICAL PHENOTYPES. EPIGENETICS IS A CRUCIAL COMPONENT OF THIS SCENARIO, AS ITS CHANGES ARE RELATED TO SPECIFIC EXPOSURES, THEREFORE POTENTIALLY ABLE TO DISPLAY THE EFFECTS OF ENVIRONMENT ON THE GENOME, FILLING THE GAP BETWEEN GENETIC ASSET AND ENVIRONMENT IN EXPLAINING DISEASE DEVELOPMENT. TO DATE, THE MOST PROMISING BIOMARKERS HAVE BEEN ASSESSED IN OCCUPATIONAL COHORTS AS WELL AS IN CASE/CONTROL STUDIES AND INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS, MICRORNA EXPRESSION, EXTRACELLULAR VESICLES, TELOMERE LENGTH, AND MITOCHONDRIAL ALTERATIONS. 2019 14 805 53 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 15 5011 44 PEROXIREDOXIN6, A MULTITASK ANTIOXIDANT ENZYME INVOLVED IN THE PATHOPHYSIOLOGY OF CHRONIC NONCOMMUNICABLE DISEASES. SIGNIFICANCE: CHRONIC NONCOMMUNICABLE DISEASES (NCDS) ARE THE LEADING CAUSES OF DISABILITY AND DEATH WORLDWIDE. NCDS MAINLY COMPRISE DIABETES MELLITUS, CARDIOVASCULAR DISEASES, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CANCER, AND NEUROLOGICAL DEGENERATIVE DISEASES, WHICH KILL MORE THAN 80% OF POPULATION, ESPECIALLY THE ELDERLY, WORLDWIDE. RECENT ADVANCES: SEVERAL RECENT THEORIES ESTABLISHED NCDS AS MULTIFACTORIAL DISEASES, WHERE A COMBINATION OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS CONTRIBUTES TO THEIR PATHOGENESIS. NEVERTHELESS, RECENT FINDINGS SUGGEST THAT THE COMMON FACTOR LINKING ALL THESE PATHOLOGIES IS AN INCREASE IN OXIDATIVE STRESS AND THE AGE-RELATED LOSS OF THE ANTIOXIDANT MECHANISMS OF DEFENSE AGAINST IT. IMPAIRMENT IN MITOCHONDRIAL HOMEOSTASIS WITH CONSEQUENT DEREGULATION IN OXIDATIVE STRESS BALANCE HAS ALSO BEEN SUGGESTED. CRITICAL ISSUES: THEREFORE, ANTIOXIDANT PROTEINS DESERVE PARTICULAR ATTENTION FOR THEIR POTENTIAL ROLE AGAINST NCDS. IN PARTICULAR, PEROXIREDOXIN(PRDX)6 IS A UNIQUE ANTIOXIDANT ENZYME, BELONGING TO THE PRDX FAMILY, WITH DOUBLE PROPERTIES, PEROXIDASE AND PHOSPHOLIPASE ACTIVITIES. THROUGH THESE ACTIVITIES, PRDX6 HAS BEEN SHOWN TO BE A POWERFUL ANTIOXIDANT ENZYME, IMPLICATED IN THE PATHOGENESIS OF DIFFERENT NCDS. RECENTLY, WE DESCRIBED A PHENOTYPE OF DIABETES MELLITUS IN PRDX6 KNOCKOUT MICE, SUGGESTING A PIVOTAL ROLE OF PRDX6 IN THE PATHOGENESIS OF CARDIOMETABOLIC DISEASES. FUTURE DIRECTIONS: INCREASING AWARENESS ON THE ROLE OF ANTIOXIDANT DEFENSES IN THE PATHOGENESIS OF NCDS MAY OPEN NOVEL THERAPEUTIC APPROACHES TO REDUCE THE BURDEN OF THIS PANDEMIC PHENOMENON. HOWEVER, KNOWLEDGE OF THE ROLE OF PRDX6 IN NCD PREVENTION AND PATHOGENESIS IS STILL NOT CLARIFIED. 2019 16 4168 28 MEDITERRANEAN DIET AS A TOOL TO COMBAT INFLAMMATION AND CHRONIC DISEASES. AN OVERVIEW. SINCE ANCIENT TIMES, THE QUALITY OF NOURISHMENT IS A MILESTONE FOR THE MAINTENANCE OF HEALTH AND AS IT IS STATED 'PREVENTION IS BETTER THAN CURE', AMONGST THE SO-CALLED 'HEALTHY' DIETS MEDITERRANEAN DIET (MD) CLAIMS THE LION'S SHARE. IT STANDS IN GOOD STEAD BECAUSE OF A VARIETY OF VALUABLE MACRO- AND MICRONUTRIENTS. SO, ADHERENCE TO A MD IS ASSOCIATED WITH THE REDUCTION OF INFLAMMATION AND NON-COMMUNICABLE (NCD) OR CHRONIC DISEASES. NUMEROUS STUDIES TRY TO SCRUTINIZE THE ROLE OF MD COMPONENTS AS REGARDS REDUCING INFLAMMATION, LOWERING RATE, AND MORTALITY FOR DISORDERS AND ILLNESSES, AND PREVENTING NCD. MD REGIME OF THE INHABITANTS OF THE MEDITERRANEAN BASIN INCLUDES A VARIETY OF ETHNIC NUTRITIONAL HABITS AND REGULATES AN ARRAY OF EFFECTS AND EPIGENETIC CHANGES THAT AFFECT HUMAN WELLBEING. THE RESEARCH IS STILL ONGOING AND ENDEAVORS TO ELUCIDATE EVERY ASPECT OF THIS ISSUE. THIS REVIEW FOCUSES ON THE IMPACT OF MD ON INFLAMMATION HIGHLIGHTS POSITIVE RESULTS REGARDING NCD AND INDICATES THE NEED FOR MORE HIGH-QUALITY EXPERIMENTS AND TRIALS IN ORDER TO OVERCOME ANY DISCREPANCIES. 2020 17 4080 28 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 18 372 33 AN EMERGING EPIDEMIC OF NONCOMMUNICABLE DISEASES IN DEVELOPING POPULATIONS DUE TO A TRIPLE EVOLUTIONARY MISMATCH. WITH THEIR TRANSITION FROM ADVERSE TO AFFLUENT ENVIRONMENTS, DEVELOPING POPULATIONS EXPERIENCE A RAPID INCREASE IN THE NUMBER OF INDIVIDUALS WITH NONCOMMUNICABLE DISEASES. HERE, WE EMPHASIZE THAT DEVELOPING POPULATIONS ARE MORE SUSCEPTIBLE THAN WESTERN POPULATIONS TO ACQUIRE THESE CHRONIC DISEASES, BECAUSE THEIR GENETIC, CULTURAL, AND EPIGENETIC CHARACTERISTICS DO NOT MATCH WITH THE EAGERLY AWAITED AFFLUENT ENVIRONMENTS. IN REGARD TO THIS, THERE IS AN URGENT NEED FOR PUBLIC HEALTH ORGANIZATIONS TO REORGANIZE CURRENT ENVIRONMENTS IN DEVELOPING POPULATIONS SO AS TO FIT THEIR INHERITED CHARACTERISTICS. UNFORTUNATELY, THIS NEED IS NEGLECTED AS AN ESSENTIAL PART OF THE SUSTAINABLE DEVELOPMENT GOALS THAT FORM THE CORE OF THE UNITED NATIONS' POST-2015 DEVELOPMENT AGENDA. ONLY THROUGH GLOBAL COLLABORATIVE EFFORTS CAN THE ENVIRONMENTS IN DEVELOPING POPULATIONS BE REORGANIZED AND, THEREBY, THE EMERGING EPIDEMIC OF NONCOMMUNICABLE DISEASES BE STALLED. 2016 19 2801 32 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 20 4006 32 LOST AMONG THE TREES? THE AUTONOMIC NERVOUS SYSTEM AND PAEDIATRICS. THE AUTONOMIC NERVOUS SYSTEM (ANS) HAS BEEN STRIKINGLY NEGLECTED IN WESTERN MEDICINE. DESPITE ITS PROFOUND IMPORTANCE FOR REGULATION, ADJUSTMENT AND COORDINATION OF BODY SYSTEMS, IT LACKS PRIORITY IN TRAINING AND PRACTICE AND RECEIVES SCANT ATTENTION IN NUMEROUS MAJOR TEXTBOOKS. THE ANS IS INTEGRAL TO MANIFESTATIONS OF ILLNESS, UNDERLYING FAMILIAR PHYSICAL AND PSYCHOLOGICAL SYMPTOMS. WHEN ANS ACTIVITY IS ITSELF DYSFUNCTIONAL, USUAL INDICATORS OF ACUTE ILLNESS MAY PROVE DECEPTIVE. RECOGNISING THE RELEVANCE OF THE ANS CAN INVOLVE SEEING THE FAMILIAR THROUGH FRESH EYES, CHALLENGING ASSUMPTIONS IN CLINICAL ASSESSMENT AND IN APPROACHES TO PRACTICE. ITS IMPORTANCE EXTENDS FROM PHYSICAL AND PSYCHOLOGICAL WELL-BEING TO PARENTING AND SAFEGUARDING, PUBLIC SERVICES AND THE FUNCTIONING OF SOCIETY. EXPLORATION OF ITS ROLE IN CONDITIONS RANGING FROM NEUROLOGICAL, GASTROINTESTINAL AND CONNECTIVE TISSUE DISORDERS, DIABETES AND CHRONIC FATIGUE SYNDROME, TO AUTISM, BEHAVIOURAL AND MENTAL HEALTH DIFFICULTIES MAY OPEN THERAPEUTIC AVENUES. THE ANS OFFERS A MECHANISM FOR SO-CALLED FUNCTIONAL ILLNESSES AND ILLUSTRATES THE IMPORTANCE OF RECOGNISING THAT 'STRESS' TAKES MANY FORMS, PHYSICAL, PSYCHOLOGICAL AND ENVIRONMENTAL, DESIRABLE AND OTHERWISE. EVIDENCE OF INTRAUTERINE AND POST-NATAL PROGRAMMING OF ANS REACTIVITY SUGGESTS THAT NEONATAL CARE AND SAFEGUARDING PRACTICE MAY OFFER PREVENTIVE OPPORTUNITY, AS MAY GREATER UNDERSTANDING OF EPIGENETIC CHANGE OF ANS ACTIVITY THROUGH, FOR EXAMPLE, ACCIDENTAL OR PSYCHOLOGICAL TRAUMA OR INFECTION. THE AIM OF THIS ARTICLE IS TO ACCELERATE RECOGNITION OF THE IMPORTANCE OF THE ANS THROUGHOUT PAEDIATRICS, AND OF THE POTENTIAL PHYSICAL AND PSYCHOLOGICAL COST OF NEGLECTING IT. 2014