1 3901 187 LEAD (PB) AND NEURODEVELOPMENT: A REVIEW ON EXPOSURE AND BIOMARKERS OF EFFECT (BDNF, HDL) AND SUSCEPTIBILITY. LEAD (PB) IS A UBIQUITOUS ENVIRONMENTAL POLLUTANT AND A POTENT TOXIC COMPOUND. HUMANS ARE EXPOSED TO PB THROUGH INHALATION, INGESTION, AND SKIN CONTACT VIA FOOD, WATER, TOBACCO SMOKE, AIR, DUST, AND SOIL. PB ACCUMULATES IN BONES, BRAIN, LIVER AND KIDNEY. FETAL EXPOSURE OCCURS VIA TRANSPLACENTAL TRANSMISSION. THE MOST CRITICAL HEALTH EFFECTS ARE DEVELOPMENTAL NEUROTOXICITY IN INFANTS AND CARDIOVASCULAR EFFECTS AND NEPHROTOXICITY IN ADULTS. PB EXPOSURE HAS BEEN STEADILY DECREASING OVER THE PAST DECADES, BUT THERE ARE FEW RECENT EXPOSURE DATA FROM THE GENERAL EUROPEAN POPULATION; MOREOVER, NO SAFE PB LIMIT HAS BEEN SET. SENSITIVE BIOMARKERS OF EXPOSURE, EFFECT AND SUSCEPTIBILITY, THAT RELIABLY AND TIMELY INDICATE PB-ASSOCIATED TOXICITY ARE REQUIRED TO ASSESS HUMAN EXPOSURE-HEALTH RELATIONSHIPS IN A SITUATION OF LOW TO MODERATE EXPOSURE. THEREFORE, A SYSTEMATIC LITERATURE REVIEW BASED ON PUBMED ENTRIES PUBLISHED BEFORE JULY 2019 THAT ADDRESSED PB EXPOSURE AND BIOMARKERS OF EFFECT AND SUSCEPTIBILITY, NEURODEVELOPMENTAL TOXICITY, EPIGENETIC MODIFICATIONS, AND TRANSCRIPTOMICS WAS CONDUCTED. FINALLY INCLUDED WERE 58 ORIGINAL PAPERS ON PB EXPOSURE AND 17 STUDIES ON BIOMARKERS. THE BIOMARKERS THAT ARE LINKED TO PB EXPOSURE AND NEURODEVELOPMENT WERE GROUPED INTO EFFECT BIOMARKERS (SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND SERUM/SALIVA CORTISOL), SUSCEPTIBILITY MARKERS (EPIGENETIC MARKERS AND GENE SEQUENCE VARIANTS) AND OTHER BIOMARKERS (SERUM HIGH-DENSITY LIPOPROTEIN (HDL), MATERNAL IRON (FE) AND CALCIUM (CA) STATUS). SERUM BDNF AND PLASMA HDL ARE POTENTIAL CANDIDATES TO BE FURTHER VALIDATED AS EFFECT MARKERS FOR ROUTINE USE IN HBM STUDIES OF PB, COMPLEMENTED BY MARKERS OF FE AND CA STATUS TO ALSO ADDRESS NUTRITIONAL INTERACTIONS RELATED TO NEURODEVELOPMENTAL DISORDERS. FOR SEVERAL MARKERS, A CAUSAL RELATIONSHIP WITH PB-INDUCED NEURODEVELOPMENTAL TOXICITY IS LIKELY. RESULTS ON BDNF ARE DISCUSSED IN RELATION TO ADVERSE OUTCOME PATHWAY (AOP) 13 ("CHRONIC BINDING OF ANTAGONIST TO N-METHYL-D-ASPARTATE RECEPTORS (NMDARS) DURING BRAIN DEVELOPMENT INDUCES IMPAIRMENT OF LEARNING AND MEMORY ABILITIES") OF THE AOP-WIKI. FURTHER STUDIES ARE NEEDED TO VALIDATE SENSITIVE, RELIABLE, AND TIMELY EFFECT BIOMARKERS, ESPECIALLY FOR LOW TO MODERATE PB EXPOSURE SCENARIOS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
2  338  41 ALTERATIONS IN GENE EXPRESSION DUE TO CHRONIC LEAD EXPOSURE INDUCE BEHAVIORAL CHANGES. LEAD (PB) IS A POLLUTANT COMMONLY FOUND IN THE ENVIRONMENT, DESPITE THE IMPLEMENTATION OF PUBLIC HEALTH POLICIES INTENDED TO REMOVE IT. DUE TO ITS CHEMICAL CHARACTERISTICS AS A DIVALENT ION, PB INTERACTS WITH CELLS, ENZYMES, AND TISSUES, CAUSING PATHOLOGICAL, PHYSICAL, AND BEHAVIORAL ALTERATIONS. RECENT BIOTECHNOLOGICAL ADVANCES HAVE HELPED US TO UNDERSTAND THE MECHANISMS UNDERLYING THE DAMAGE CAUSED BY PB IN HUMAN POPULATIONS AND IN EXPERIMENTAL MODELS, AND NEW EVIDENCE ON THE EPIGENETIC ALTERATIONS CAUSED BY EXPOSITION TO ENVIRONMENTAL PB IS AVAILABLE. IT IS KNOWN THAT PB EXPOSURE IMPACTS ON BEHAVIOR (CAUSING AGGRESSIVENESS, ANXIETY, AND DEPRESSION), LEADING TO LEARNING DEFICIT AND LOCOMOTOR ACTIVITY ALTERATIONS, AND ITS PRESENCE HAS BEEN LINKED WITH THE ABNORMAL RELEASE OF NEUROTRANSMITTERS AND OTHER BIOCHEMICAL CHANGES INVOLVED IN THESE DISORDERS. STILL, FURTHER REDUCTIONIST STUDIES ARE REQUIRED TO DETERMINE THE EFFECTS OF PB EXPOSURE ON DNA AND PROTEIN EXPRESSION AND UNDERSTAND THE PROCESSES UNDERLYING THE DISEASES CAUSED BY PB. THIS WILL ALSO INDICATE POSSIBLE THERAPEUTIC TARGETS TO OFFSET THE NEGATIVE EFFECTS OF THE HEAVY METAL. BY ELUCIDATING THE EPIGENETIC CHANGES INVOLVED, IT WOULD BE POSSIBLE TO MANIPULATE THEM AND PROPOSE NOVEL THERAPEUTIC APPROACHES IN THIS AREA. THIS REVIEW IS AIMED TO PROVIDE AN OVERVIEW OF STUDIES THAT LINK PB EXPOSURE TO BEHAVIORAL CHANGES, AS WELL AS BIOCHEMICAL AND EPIGENETIC ALTERATIONS AT A NEUROTRANSMITTER LEVEL, CONSIDERING THE IMPORTANCE OF THIS METAL IN BEHAVIOR ABNORMALITIES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
3  228  45 ADAPTATION OF THE HUMAN POPULATION TO THE ENVIRONMENT: CURRENT KNOWLEDGE, CLUES FROM CZECH CYTOGENETIC AND "OMICS" BIOMONITORING STUDIES AND POSSIBLE MECHANISMS. THE HUMAN POPULATION IS CONTINUALLY EXPOSED TO NUMEROUS HARMFUL ENVIRONMENTAL STRESSORS, CAUSING NEGATIVE HEALTH EFFECTS AND/OR DEREGULATION OF BIOMARKER LEVELS. HOWEVER, STUDIES REPORTING NO OR EVEN POSITIVE IMPACTS OF SOME STRESSORS ON HUMANS ARE ALSO SOMETIMES PUBLISHED. THE MAIN AIM OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF THE LAST DECADE OF CZECH BIOMONITORING RESEARCH, CONCERNING THE EFFECT OF VARIOUS LEVELS OF AIR POLLUTION (BENZO[A]PYRENE) AND RADIATION (URANIUM, X-RAY EXAMINATION AND NATURAL RADON BACKGROUND), ON THE DIFFERENTLY EXPOSED POPULATION GROUPS. BECAUSE SOME RESULTS OBTAINED FROM CYTOGENETIC STUDIES WERE OPPOSITE THAN HYPOTHESIZED, WE HAVE SEARCHED FOR A MEANINGFUL INTERPRETATION IN GENOMIC/EPIGENETIC STUDIES. A DETAILED ANALYSIS OF OUR DATA SUPPORTED BY THE STUDIES OF OTHERS AND CURRENT EPIGENETIC KNOWLEDGE, LEADS TO A HYPOTHESIS OF THE VERSATILE MECHANISM OF ADAPTATION TO ENVIRONMENTAL STRESSORS VIA DNA METHYLATION SETTINGS WHICH MAY EVEN ORIGINATE IN PRENATAL DEVELOPMENT, AND HELP TO REDUCE THE RESULTING DNA DAMAGE LEVELS. THIS HYPOTHESIS IS FULLY IN AGREEMENT WITH UNEXPECTED DATA FROM OUR STUDIES (E.G. LOWER LEVELS OF DNA DAMAGE IN SUBJECTS FROM HIGHLY POLLUTED REGIONS THAN IN CONTROLS OR IN SUBJECTS EXPOSED REPEATEDLY TO A POLLUTANT THAN IN THOSE WITHOUT PREVIOUS EXPOSURE), AND IS ALSO SUPPORTED BY DIFFERENCES IN DNA METHYLATION PATTERNS IN GROUPS FROM REGIONS WITH VARIOUS LEVELS OF POLLUTION. IN LIGHT OF THE ADAPTATION HYPOTHESIS, THE FOLLOWING POINTS MAY BE SUGGESTED FOR FUTURE RESEARCH: (I) THE CHRONIC AND ACUTE EXPOSURE OF STUDY SUBJECTS SHOULD BE DISTINGUISHED; (II) THE EXPOSURE HISTORY SHOULD BE MAPPED INCLUDING PLACE OF RESIDENCE DURING THE LIFE AND PRENATAL DEVELOPMENT; (III) CHANGES OF EPIGENETIC MARKERS SHOULD BE MONITORED OVER TIME. IN SUMMARY, INVESTIGATION OF HUMAN ADAPTATION TO THE ENVIRONMENT, ONE OF THE MOST IMPORTANT PROCESSES OF SURVIVAL, IS A NEW CHALLENGE FOR FUTURE RESEARCH IN THE FIELD OF HUMAN BIOMONITORING THAT MAY CHANGE OUR VIEW ON THE RESULTS OF BIOMARKER ANALYSES AND POTENTIAL NEGATIVE HEALTH IMPACTS OF THE ENVIRONMENT.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
4 5194  43 PRENATAL EXPOSURE TO POTENTIALLY TOXIC METALS AND THEIR EFFECTS ON GENETIC MATERIAL IN OFFSPRING: A SYSTEMATIC REVIEW. IN RECENT YEARS, THE BACKGROUND LEVEL OF ENVIRONMENTAL POLLUTANTS, INCLUDING METALS, HAS INCREASED. POLLUTANT EXPOSURE DURING THE EARLIEST STAGES OF LIFE MAY DETERMINE CHRONIC DISEASE SUSCEPTIBILITY IN ADULTHOOD BECAUSE OF GENETIC OR EPIGENETIC CHANGES. THE OBJECTIVE OF THIS REVIEW WAS TO IDENTIFY THE ASSOCIATION BETWEEN PRENATAL AND EARLY POSTNATAL EXPOSURE TO POTENTIALLY TOXIC METALS (PTMS) AND THEIR ADVERSE EFFECTS ON THE GENETIC MATERIAL OF OFFSPRING. A SYSTEMATIC REVIEW WAS CARRIED OUT FOLLOWING THE COCHRANE METHODOLOGY IN FOUR DATABASES: PUBMED, SCOPUS, WEB OF SCIENCE, AND THE COCHRANE LIBRARY. ELIGIBLE PAPERS WERE THOSE CONDUCTED IN HUMANS AND PUBLISHED IN ENGLISH BETWEEN 2010/01/01 AND 2021/04/30. A TOTAL OF 57 ARTICLES WERE INCLUDED, MOST OF WHICH EVALUATED PRENATAL EXPOSURE. MOST COMMONLY EVALUATED PTMS WERE AS, CD, AND PB. MAIN ADVERSE EFFECTS ON THE GENETIC MATERIAL OF NEWBORNS ASSOCIATED WITH PTM PRENATAL EXPOSURE WERE ALTERATIONS IN TELOMERE LENGTH, GENE OR PROTEIN EXPRESSION, MITOCHONDRIAL DNA CONTENT, METABOLOMICS, DNA DAMAGE, AND EPIGENETIC MODIFICATIONS. MANY OF THESE EFFECTS WERE SEX-SPECIFIC, BEING PREDOMINANT IN BOYS. ONE ARTICLE REPORTED A SYNERGISTIC INTERACTION BETWEEN AS AND HG, AND TWO ARTICLES OBSERVED ANTAGONISTIC INTERACTIONS BETWEEN PTMS AND ESSENTIAL METALS, SUCH AS CU, SE, AND ZN. THE FINDINGS IN THIS REVIEW HIGHLIGHT THAT THE PROBLEM OF PTM EXPOSURE PERSISTS, AFFECTING THE MOST SUSCEPTIBLE POPULATIONS, SUCH AS NEWBORNS. SOME OF THESE ASSOCIATIONS WERE OBSERVED AT LOW CONCENTRATIONS OF PTMS. MOST OF THE STUDIES HAVE FOCUSED ON SINGLE EXPOSURES; HOWEVER, THREE INTERACTIONS BETWEEN ESSENTIAL AND NONESSENTIAL METALS WERE OBSERVED, HIGHLIGHTING THAT METAL MIXTURES NEED MORE ATTENTION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
5 6781  53 [BREATHING: AMBIENT AIR POLLUTION AND HEALTH - PART III]. THE THIRD PART OF THE DGP STATEMENT INTRODUCES THE CURRENT BODY OF KNOWLEDGE ON LESS STUDIED HEALTH OUTCOMES ASSOCIATED WITH EXPOSURE TO AMBIENT AIR POLLUTION: THE NEGATIVE IMPACT ON METABOLISM LEADING TO IMPAIRED GLUCOSE TOLERANCE AND DIABETES AS WELL AS CONTRIBUTION TO THE DEVELOPMENT OF NEURODEGENERATIVE DISORDERS AND DELAYED COGNITIVE FUNCTION IN CHILDREN. FURTHERMORE, PRENATAL EXPOSURE AND ADVERSE EFFECTS ON MOTHER AND CHILD ARE ADDRESSED. FINALLY, THE CURRENTLY DISCUSSED BIOLOGICAL MECHANISMS UNDERLYING VARIOUS HEALTH EFFECTS ASSOCIATED WITH EXPOSURE TO AIR POLLUTION ARE DESCRIBED.DIFFERING, BUT OFTEN COMPLEMENTARY BIOLOGICAL MECHANISMS CREATE THE BASIS FOR THE DIVERSE HEALTH OUTCOMES CAUSED BY AIR POLLUTION. OXIDATIVE STRESS AND A SUBCLINICAL INFLAMMATORY RESPONSE IN THE LUNGS AND ON A SYSTEMIC LEVEL ("LOW-GRADE SYSTEMIC INFLAMMATION") ARE CONSIDERED TO BE KEY MECHANISMS. THEY PROMOTE SECONDARY ALTERATIONS IN THE BODY, SUCH AS VASCULAR OR METABOLIC PROCESSES, AND MAY ALSO RESULT IN THE CURRENTLY STUDIED EPIGENETIC PHENOMENA OR NEUROINFLAMMATION. IN THIS CONTEXT, THE HEALTH SIGNIFICANCE OF SOLUBLE PARTICULATE MATTER AND THE ROLE OF ULTRAFINE PARTICLES TRANSLOCATED ACROSS BIOLOGICAL MEMBRANES INTO BLOOD VESSEL AND TRANSPORTED VIA THE CIRCULATION TO SECONDARY TARGET ORGANS, SUCH AS LIVER, BRAIN OR THE FETUS, ARE INTENSIVELY DISCUSSED.DIABETES IS ONE OF THE LEADING CHRONIC DISEASES WORLDWIDE, WITH A PREVALENCE OF ALMOST 14 % IN GERMANY. ALTHOUGH LIFESTYLE FACTORS ARE THE MAIN CAUSES, CURRENT EVIDENCE SUGGESTS THAT LONG-TERM EXPOSURE TO AIR POLLUTION MAY ADDITIONALLY INCREASE THE RISK FOR TYPE 2 DIABETES. SUPPORTING EVIDENCE FOR A CAUSAL ROLE OF AIR POLLUTION IS PROVIDED BY STUDIES ADDRESSING THE REGULATION OF THE BLOOD GLUCOSE LEVELS IN METABOLICALLY HEALTHY PARTICIPANTS, INSULIN SENSITIVITY, OR PREGNANCY-RELATED DIABETES. EXPERIMENTAL STUDIES PROVIDE FURTHER SUPPORT FOR PLAUSIBLE BIOLOGICAL MECHANISMS. HOWEVER, PROSPECTIVE STUDIES ARE NEEDED TO GAIN MORE EVIDENCE, TAKING MULTIPLE LIFESTYLE AND ENVIRONMENTAL FACTORS, SUCH AS GREEN SPACE AND NOISE, AND AN IMPROVED INDIVIDUAL EXPOSURE ASSESSMENT INTO ACCOUNT.THE AGING POPULATION HAS AN INCREASED RISK OF NEURODEGENERATIVE DISEASES. FIRST STUDIES POINT TOWARDS A CONTRIBUTION OF CHRONIC EXPOSURE TO AIR POLLUTION, SPECIFICALLY BY PARTICULATE MATTER. SEVERAL STUDIES REPORT ITS ASSOCIATION WITH DECREASED NEUROCOGNITIVE CAPACITY OR AN INCREASED PREVALENCE OF DEMENTIA OR ALZHEIMER'S DISEASE IN ADULTS. HOWEVER, THE STUDIES ARE INHOMOGENEOUS REGARDING DESIGN, EXPOSURE AND OUTCOME, LEADING TO INCONSISTENT RESULTS. WITH RESPECT TO THE INFLUENCE ON NEUROCOGNITIVE DEVELOPMENT OF CHILDREN, FIRST STUDIES SUGGEST AN ASSOCIATION BETWEEN THE LEVEL OF AIR POLLUTION, E. G. AT SCHOOL, AND DELAYED COGNITIVE DEVELOPMENT.EVEN THOUGH THE EVIDENCE FOR THE DIFFERENT BIOLOGICAL ENDPOINTS DURING PREGNANCY IS STILL HETEROGENEOUS, THE STUDIES GENERALLY POINT TOWARDS AN ADVERSE IMPACT OF AIR POLLUTION ON THE MATERNAL AND FETAL ORGANISMS. THE STRONGEST EVIDENCE EXISTS FOR LOW BIRTH WEIGHT, WITH SMALL EFFECT SIZES OF ONLY SOME GRAMS, AND FOR A HIGHER INCIDENCE OF REDUCED BIRTH WEIGHT (< 2500 G). AN INCREASED RISK FOR GESTATIONAL HYPERTENSION AND PREECLAMPSIA UNDERSCORES THE POSSIBLE IMPACT OF EXPOSURE TO AIR POLLUTION ON THE MATERNAL ORGANISM. HOWEVER, THE CURRENT BODY OF EVIDENCE DOES NOT YET ALLOW A FINAL CONCLUSION ON THE INFLUENCE OF INTRAUTERINE EXPOSURE TO AIR POLLUTION REGARDING EARLY CHILDHOOD LUNG FUNCTION AND DEVELOPMENT OF ALLERGIES, PARTICULARLY IN LIGHT OF THE FACT THAT IT IS HARD TO DISTINGUISH IN EPIDEMIOLOGICAL STUDIES BETWEEN THE EFFECTS OF PRE- AND POSTNATAL EXPOSURE.	2019	

6 2677  29 EVALUATING THE CHALLENGES AND REPRODUCIBILITY OF STUDIES INVESTIGATING DNA METHYLATION SIGNATURES OF PSYCHOLOGICAL STRESS. PSYCHOLOGICAL STRESS CAN INCREASE THE RISK OF A WIDE RANGE OF NEGATIVE HEALTH OUTCOMES. STUDIES HAVE BEEN COMPLETED TO DETERMINE IF DNA METHYLATION CHANGES OCCUR IN THE HUMAN BRAIN BECAUSE OF STRESS AND ARE ASSOCIATED WITH LONG-TERM EFFECTS AND DISEASE, BUT RESULTS HAVE BEEN INCONSISTENT. HUMAN CANDIDATE GENE STUDIES (150) AND EPIGENOME-WIDE ASSOCIATION STUDIES (67) WERE SYSTEMATICALLY EVALUATED TO ASSESS HOW DNA METHYLATION IS IMPACTED BY STRESS DURING THE PRENATAL PERIOD, EARLY CHILDHOOD AND ADULTHOOD. THE ASSOCIATION BETWEEN DNA METHYLATION OF NR3C1 EXON 1F AND CHILD MALTREATMENT AND EARLY LIFE ADVERSITY WAS WELL DEMONSTRATED, BUT OTHER GENES DID NOT EXHIBIT A CLEAR ASSOCIATION. THE REPRODUCIBILITY OF INDIVIDUAL CPG SITES IN EPIGENOME-WIDE ASSOCIATION STUDIES WAS ALSO POOR. HOWEVER, BIOLOGICAL PATHWAYS, INCLUDING STRESS RESPONSE, BRAIN DEVELOPMENT AND IMMUNITY, HAVE BEEN CONSISTENTLY IDENTIFIED ACROSS DIFFERENT STRESSORS THROUGHOUT THE LIFE SPAN. FUTURE STUDIES WOULD BENEFIT FROM THE INCREASED SAMPLE SIZE, LONGITUDINAL DESIGN, STANDARDIZED METHODOLOGY, OPTIMAL QUALITY CONTROL, AND IMPROVED STATISTICAL PROCEDURES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
7 1324  36 DEOXYRIBONUCLEIC ACID (DNA) METHYLATION IN CHILDREN EXPOSED TO AIR POLLUTION: A POSSIBLE MECHANISM UNDERLYING RESPIRATORY HEALTH EFFECTS DEVELOPMENT. AIR POLLUTION IS A SUBSTANTIAL ENVIRONMENTAL THREAT TO CHILDREN AND ACTS AS ACUTE AND CHRONIC DISEASE RISK FACTORS ALIKE. SEVERAL STUDIES HAVE PREVIOUSLY EVALUATED EPIGENETIC MODIFICATIONS CONCERNING ITS EXPOSURE ACROSS VARIOUS LIFE STAGES. HOWEVER, FINDINGS ON EPIGENETIC MODIFICATIONS AS THE CONSEQUENCES OF AIR POLLUTION DURING CHILDHOOD ARE RATHER MINIMAL. THIS REVIEW EVALUATED HIGHLY RELEVANT STUDIES IN THE FIELD TO ANALYZE THE EXISTING LITERATURE REGARDING EXPOSURE TO AIR POLLUTION, WITH A FOCUS ON EPIGENETIC ALTERATIONS DURING CHILDHOOD AND THEIR CONNECTIONS WITH RESPIRATORY HEALTH EFFECTS. THE SEARCH WAS CONDUCTED USING READILY AVAILABLE ELECTRONIC DATABASES (PUBMED AND SCIENCEDIRECT) TO SCREEN FOR CHILDREN'S STUDIES ON EPIGENETIC MECHANISMS FOLLOWING EITHER PRE- OR POST-NATAL EXPOSURE TO AIR POLLUTANTS. STUDIES RELEVANT ENOUGH AND MATCHED THE PREDETERMINED CRITERIA WERE CHOSEN TO BE REVIEWED. NON-ENGLISH ARTICLES AND STUDIES THAT DID NOT REPORT BOTH AIR MONITORING AND EPIGENETIC OUTCOMES IN THE SAME ARTICLE WERE EXCLUDED. THE REVIEW FOUND THAT EPIGENETIC CHANGES HAVE BEEN LINKED WITH EXPOSURE TO AIR POLLUTANTS DURING EARLY LIFE WITH EVIDENCE AND REPORTS OF HOW THEY MAY DEREGULATE THE EPIGENOME BALANCE, THUS INDUCING DISEASE PROGRESSION IN THE FUTURE. EPIGENETIC STUDIES EVOLVE AS A PROMISING NEW APPROACH IN DECIPHERING THE UNDERLYING IMPACTS OF AIR POLLUTION ON DEOXYRIBONUCLEIC ACID (DNA) DUE TO LINKS ESTABLISHED BETWEEN SOME OF THESE EPIGENETIC MECHANISMS AND ILLNESSES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
8 2021  31 EPIGENETIC CHANGES ASSOCIATED WITH DIFFERENT TYPES OF STRESSORS AND SUICIDE. STRESS IS ASSOCIATED WITH VARIOUS EPIGENETIC CHANGES. SOME STRESS-INDUCED EPIGENETIC CHANGES ARE HIGHLY DYNAMIC, WHEREAS OTHERS ARE ASSOCIATED WITH LASTING MARKS ON THE EPIGENOME. IN OUR STUDY, A COMPREHENSIVE NARRATIVE REVIEW OF THE LITERATURE WAS PERFORMED BY INVESTIGATING THE EPIGENETIC CHANGES THAT OCCUR WITH ACUTE STRESS, CHRONIC STRESS, EARLY CHILDHOOD STRESS, AND TRAUMATIC STRESS EXPOSURES, ALONG WITH EXAMINING THOSE OBSERVED IN POST-MORTEM BRAINS OR BLOOD SAMPLES OF SUICIDE COMPLETERS AND ATTEMPTERS. IN ADDITION, THE TRANSGENERATIONAL EFFECTS OF THESE CHANGES ARE REPORTED. FOR ALL TYPES OF STRESS STUDIES EXAMINED, THE GENES NR3C1, OXTR, SLC6A4, AND BDNF REPRODUCIBLY SHOWED EPIGENETIC CHANGES, WITH SOME MODIFICATIONS OBSERVED TO BE PASSED DOWN TO SUBSEQUENT GENERATIONS FOLLOWING STRESS EXPOSURES. THE AFOREMENTIONED GENES ARE KNOWN TO BE INVOLVED IN NEURONAL DEVELOPMENT AND HORMONAL REGULATION AND ARE ALL ASSOCIATED WITH SUSCEPTIBILITY TO MENTAL HEALTH DISORDERS INCLUDING DEPRESSION, ANXIETY, PERSONALITY DISORDERS, AND PTSD (POST-TRAUMATIC STRESS DISORDER). FURTHER RESEARCH IS WARRANTED IN ORDER TO DETERMINE THE SCOPE OF EPIGENETIC ACTIONABLE TARGETS IN INDIVIDUALS SUFFERING FROM THE LONG-LASTING EFFECTS OF STRESSFUL EXPERIENCES.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
9 2075  29 EPIGENETIC DIFFERENCES IN INFLAMMATION GENES OF MONOZYGOTIC TWINS ARE RELATED TO PARENT-CHILD EMOTIONAL AVAILABILITY AND HEALTH. THE INFLAMMATORY RESPONSE IS AN IMMUNE DEFENSE ENGAGED IMMEDIATELY AFTER INJURY OR INFECTION. CHRONIC INFLAMMATION CAN BE DELETERIOUS FOR VARIOUS HEALTH OUTCOMES AND IS CHARACTERIZED BY HIGH LEVELS OF PRO-INFLAMMATORY MARKERS SUCH AS C-REACTIVE PROTEIN (CRP), INTERLEUKIN 6 (IL-6), AND TUMOR NECROSIS FACTOR ALPHA (TNF-ALPHA). A LARGE BODY OF RESEARCH DEMONSTRATES THESE INFLAMMATORY MARKERS ARE RESPONSIVE TO STRESS AND QUALITY OF SOCIAL RELATIONSHIPS THROUGHOUT THE LIFESPAN. FOR EXAMPLE, THE QUALITY OF THE EARLY PARENTAL BOND PREDICTS VARIOUS HEALTH OUTCOMES AND MAY BE DRIVEN BY CHANGES IN IMMUNE FUNCTION. EPIGENETIC PROCESSES, SUCH AS DNA METHYLATION, MAY BE ONE MECHANISM BY WHICH EARLY SOCIAL EXPERIENCES SHAPE IMMUNE FUNCTIONING. THE PRESENT STUDY USED A MONOZYGOTIC TWIN DIFFERENCE DESIGN TO ASSESS IF MOTHER-REPORTED EMOTIONAL AVAILABILITY AT 1 YEAR AND 2.5 YEARS PREDICTED IMMUNE GENE METHYLATION AT 8 YEARS OF AGE. FURTHER, WE ASSESSED IF INFLAMMATION GENE METHYLATION WAS RELATED TO GENERAL HEALTH PROBLEMS (E.G. INFECTIONS, ALLERGIES, ETC.). WE FOUND THAT MOTHER-REPORTED EMOTIONAL AVAILABILITY AT 1 YEAR, BUT NOT 2.5 YEARS, WAS RELATED TO METHYLATION OF VARIOUS IMMUNE GENES IN MONOZYGOTIC TWINS. FURTHERMORE, TWIN PAIRS DISCORDANT IN HEALTH PROBLEMS HAVE MORE DIFFERENCE IN IMMUNE GENE METHYLATION COMPARED TO TWIN PAIRS CONCORDANT FOR HEALTH PROBLEMS, SUGGESTING THAT METHYLATION OF IMMUNE GENES MAY HAVE FUNCTIONAL CONSEQUENCES FOR GENERAL HEALTH. THESE RESULTS SUGGEST THAT THE EMOTIONAL COMPONENT OF ATTACHMENT QUALITY DURING INFANCY CONTRIBUTES TO IMMUNE EPIGENETIC PROFILES IN CHILDHOOD, WHICH MAY INFLUENCE GENERAL HEALTH.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
10 6159  43 THE GENETICS AND EPIGENETICS OF FATIGUE. FATIGUE IS A COMMON SYMPTOM AND INCLUDES BOTH PHYSICAL AND MENTAL COMPONENTS. IT CAN BE ASSOCIATED WITH A VARIETY OF DIFFERENT SYNDROMES AND DISEASES, BUT IN MANY CASES IS NOT ASSOCIATED WITH OTHER COMORBID CONDITIONS. MOST HUMANS HAVE EXPERIENCED ACUTE FATIGUE IN RELATION TO DIFFERENT STRESSORS. ACUTE FATIGUE TYPICALLY DECREASES AS THE EFFECT OF THE TRIGGERING FACTOR IS REDUCED AND A NORMAL HOMEOSTATIC BALANCE IS RESTORED. FATIGUE THAT PERSISTS FOR 6 MONTHS OR MORE IS TERMED CHRONIC FATIGUE. CHRONIC FATIGUE (CF) IN COMBINATION WITH A MINIMUM OF 4 OF 8 SYMPTOMS AND THE ABSENCE OF DISEASES THAT COULD EXPLAIN THESE SYMPTOMS, CONSTITUTE THE CASE DEFINITION FOR CHRONIC FATIGUE SYNDROME. IN SPITE OF ITS PREVALENCE, THE BIOLOGY OF FATIGUE IS RELATIVELY POORLY UNDERSTOOD AND BIOLOGICAL MARKERS HAVE NOT YET BEEN IDENTIFIED. THIS LITERATURE SEARCH WAS PERFORMED IN PUBMED TO IDENTIFY RESEARCH ON THE GENETICS AND EPIGENETICS OF FATIGUE. PUBLICATIONS WERE INCLUDED IF FATIGUE WAS A MAJOR TOPIC AND THE TOPIC WAS COMBINED WITH GENETIC AND/OR EPIGENETIC MEASUREMENTS IN ADULT HUMANS. A TOTAL OF 40 PUBLICATIONS WERE IDENTIFIED. ALTHOUGH ALTERED FUNCTIONING IN THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS, THE SEROTONERGIC SYSTEM, AND ASSOCIATIONS WITH INFECTIOUS AGENTS HAVE BEEN IDENTIFIED, THE SEARCH FOR GENETIC OR EPIGENETIC MARKERS OF FATIGUE, EITHER IN THE CONTEXT OF CF OR CHRONIC FATIGUE SYNDROME (CFS) HAS BEEN RELATIVELY UNPRODUCTIVE OR, IN THE CASE OF EPIGENETICS, NONEXISTENT. ALTHOUGH SEVERAL STUDIES, BOTH HYPOTHESIS-TESTING AND HYPOTHESIS-GENERATING, HAVE BEEN PERFORMED TO SEARCH FOR BIOMARKERS, THEY HAVE MOSTLY BEEN UNDERPOWERED, RESTRICTED BY THE HETEROGENEITY OF THE PHENOTYPE, OR LIMITED BY AN UNSYSTEMATIC STUDY DESIGN. TO BE ABLE TO CONFIRM THE HYPOTHESIS THAT RISK FOR, OR LEVELS OF, FATIGUE ARE INFLUENCED BY THE GENETIC OR EPIGENETIC BACKGROUND OF AN INDIVIDUAL, STUDIES NEED TO BE BASED ON LARGER SAMPLE SIZES WITH A MORE CLEARLY DEFINED PHENOTYPE. STUDIES NEED TO FOCUS NOT ONLY ON THE INFLUENCE OF A SINGLE ASPECT SUCH AS SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) OR DIFFERENTIAL GENE EXPRESSION ON DISEASE RISK OR STATE, BUT ALSO ON THE SYSTEMS BIOLOGY BEHIND THE DISEASE IN COMBINATION WITH INFORMATION ON ENVIRONMENTAL INFLUENCES AND VALIDATION OF FINDINGS IN FUNCTIONAL STUDIES.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
11 3106  38 GENOMICS AND THE RESPIRATORY EFFECTS OF AIR POLLUTION EXPOSURE. ADVERSE HEALTH EFFECTS FROM AIR POLLUTANTS REMAIN IMPORTANT, DESPITE IMPROVEMENT IN AIR QUALITY IN THE PAST FEW DECADES. THE EXACT MECHANISMS OF LUNG INJURY FROM EXPOSURE TO AIR POLLUTANTS ARE NOT YET FULLY UNDERSTOOD. STUDYING THE GENOME (E.G. SINGLE-NUCLEOTIDE POLYMORPHISMS (SNP) ), EPIGENOME (E.G. METHYLATION OF GENES), TRANSCRIPTOME (MRNA EXPRESSION) AND MICRORNAOME (MICRORNA EXPRESSION) HAS THE POTENTIAL TO IMPROVE OUR UNDERSTANDING OF THE ADVERSE EFFECTS OF AIR POLLUTANTS. GENOME-WIDE ASSOCIATION STUDIES OF SNP HAVE DETECTED SNP ASSOCIATED WITH RESPIRATORY PHENOTYPES; HOWEVER, TO DATE, ONLY CANDIDATE GENE STUDIES OF AIR POLLUTION EXPOSURE HAVE BEEN PERFORMED. CHANGES IN EPIGENETIC PROCESSES, SUCH DNA METHYLATION THAT LEADS TO GENE SILENCING WITHOUT ALTERING THE DNA SEQUENCE, OCCUR WITH AIR POLLUTANT EXPOSURE, ESPECIALLY GLOBAL AND GENE-SPECIFIC METHYLATION CHANGES. RESPIRATORY CELL LINE AND ANIMAL MODELS DEMONSTRATE DISTINCT GENE EXPRESSION SIGNATURES IN THE TRANSCRIPTOME, ARISING FROM EXPOSURE TO PARTICULATE MATTER OR OZONE. PARTICULATE MATTER AND OTHER ENVIRONMENTAL TOXINS ALTER EXPRESSION OF MICRORNA, WHICH ARE SHORT NON-CODING RNA THAT REGULATE GENE EXPRESSION. WHILE IT IS CLEARLY IMPORTANT TO CONTAIN RISING LEVELS OF AIR POLLUTION, STRATEGIES ALSO NEED TO BE DEVELOPED TO MINIMIZE THE DAMAGING EFFECTS OF AIR POLLUTANT EXPOSURE ON THE LUNG, ESPECIALLY FOR PATIENTS WITH CHRONIC LUNG DISEASE AND FOR PEOPLE AT RISK OF FUTURE LUNG DISEASE. CAREFUL STUDY OF GENOMIC RESPONSES WILL IMPROVE OUR UNDERSTANDING OF MECHANISMS OF LUNG INJURY FROM AIR POLLUTION AND ENABLE FUTURE CLINICAL TESTING OF INTERVENTIONS AGAINST THE TOXIC EFFECTS OF AIR POLLUTANTS.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
12  948  29 CHRONIC METABOLIC DERANGEMENT-INDUCED COGNITIVE DEFICITS AND NEUROTOXICITY ARE ASSOCIATED WITH REST INACTIVATION. CHRONIC METABOLIC ALTERATIONS MAY REPRESENT A RISK FACTOR FOR THE DEVELOPMENT OF COGNITIVE IMPAIRMENT, DEMENTIA, OR NEURODEGENERATIVE DISEASES. HYPERGLYCEMIA AND OBESITY ARE KNOWN TO IMPRINT EPIGENETIC MARKERS THAT COMPROMISE THE PROPER EXPRESSION OF CELL SURVIVAL GENES. HERE, WE SHOWED THAT CHRONIC HYPERGLYCEMIA (60 DAYS) INDUCED BY A SINGLE INTRAPERITONEAL INJECTION OF STREPTOZOTOCIN COMPROMISED COGNITION BY REDUCING HIPPOCAMPAL ERK SIGNALING AND BY INDUCING NEUROTOXICITY IN RATS. THE MECHANISMS APPEAR TO BE LINKED TO REDUCED ACTIVE DNA DEMETHYLATION AND DIMINISHED EXPRESSION OF THE NEUROPROTECTIVE TRANSCRIPTION FACTOR REST. THE IMPACT OF THE RELATIONSHIP BETWEEN ADIPOSITY AND DNA HYPERMETHYLATION ON REST EXPRESSION WAS ALSO DEMONSTRATED IN PERIPHERAL BLOOD MONONUCLEAR CELLS IN OBESE CHILDREN WITH REDUCED LEVELS OF BLOOD ASCORBATE. THE REVERSIBLE NATURE OF EPIGENETIC MODIFICATIONS AND THE COGNITIVE IMPAIRMENT REPORTED IN OBESE CHILDREN, ADOLESCENTS, AND ADULTS SUGGEST THAT THE CORRECTION OF THE ANTHROPOMETRY AND THE PERIPHERAL METABOLIC ALTERATIONS WOULD PROTECT BRAIN HOMEOSTASIS AND REDUCE THE RISK OF DEVELOPING NEURODEGENERATIVE DISEASES.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
13 2715  31 EXERCISE-INDUCED BIOCHEMICAL CHANGES AND THEIR POTENTIAL INFLUENCE ON CANCER: A SCIENTIFIC REVIEW. AIM: TO REVIEW AND DISCUSS THE AVAILABLE INTERNATIONAL LITERATURE REGARDING THE INDIRECT AND DIRECT BIOCHEMICAL MECHANISMS THAT OCCUR AFTER EXERCISE, WHICH COULD POSITIVELY, OR NEGATIVELY, INFLUENCE ONCOGENIC PATHWAYS. METHODS: THE PUBMED, MEDLINE, EMBASE AND COCHRANE LIBRARIES WERE SEARCHED FOR PAPERS UP TO JULY 2016 ADDRESSING BIOCHEMICAL CHANGES AFTER EXERCISE WITH A PARTICULAR REFERENCE TO CANCER. THE THREE AUTHORS INDEPENDENTLY ASSESSED THEIR APPROPRIATENESS FOR INCLUSION IN THIS REVIEW BASED ON THEIR SCIENTIFIC QUALITY AND RELEVANCE. RESULTS: 168 PAPERS WERE SELECTED AND CATEGORISED INTO INDIRECT AND DIRECT BIOCHEMICAL PATHWAYS. THE INDIRECT EFFECTS INCLUDED CHANGES IN VITAMIN D, WEIGHT REDUCTION, SUNLIGHT EXPOSURE AND IMPROVED MOOD. THE DIRECT EFFECTS INCLUDED INSULIN-LIKE GROWTH FACTOR, EPIGENETIC EFFECTS ON GENE EXPRESSION AND DNA REPAIR, VASOACTIVE INTESTINAL PEPTIDE, OXIDATIVE STRESS AND ANTIOXIDANT PATHWAYS, HEAT SHOCK PROTEINS, TESTOSTERONE, IRISIN, IMMUNITY, CHRONIC INFLAMMATION AND PROSTAGLANDINS, ENERGY METABOLISM AND INSULIN RESISTANCE. SUMMARY: EXERCISE IS ONE OF SEVERAL LIFESTYLE FACTORS KNOWN TO LOWER THE RISK OF DEVELOPING CANCER AND IS ASSOCIATED WITH LOWER RELAPSE RATES AND BETTER SURVIVAL. THIS REVIEW HIGHLIGHTS THE NUMEROUS BIOCHEMICAL PROCESSES, WHICH EXPLAIN THESE POTENTIAL ANTICANCER BENEFITS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
14 4767  34 NUCLEAR AND MITOCHONDRIAL DNA ALTERATIONS IN NEWBORNS WITH PRENATAL EXPOSURE TO CIGARETTE SMOKE. NEWBORNS EXPOSED TO MATERNAL CIGARETTE SMOKE (CS) IN UTERO HAVE AN INCREASED RISK OF DEVELOPING CHRONIC DISEASES, CANCER, AND ACQUIRING DECREASED COGNITIVE FUNCTION IN ADULTHOOD. ALTHOUGH THE LITERATURE REPORTS MANY DELETERIOUS EFFECTS ASSOCIATED WITH MATERNAL CIGARETTE SMOKING ON THE FETUS, THE MOLECULAR ALTERATIONS AND MECHANISMS OF ACTION ARE NOT YET CLEAR. SMOKING MAY ACT DIRECTLY ON NUCLEAR DNA BY INDUCING MUTATIONS OR EPIGENETIC MODIFICATIONS. RECENT STUDIES ALSO INDICATE THAT SMOKING MAY ACT ON MITOCHONDRIAL DNA BY INDUCING A CHANGE IN THE NUMBER OF COPIES TO MAKE UP FOR THE DAMAGE CAUSED BY SMOKING ON THE RESPIRATORY CHAIN AND LACK OF ENERGY. IN ADDITION, INDIVIDUAL GENETIC SUSCEPTIBILITY PLAYS A SIGNIFICANT ROLE IN DETERMINING THE EFFECTS OF SMOKING DURING DEVELOPMENT. FURTHERMORE, PRIOR EXPOSURE OF PATERNAL AND MATERNAL GAMETES TO CIGARETTE SMOKE MAY AFFECT THE HEALTH OF THE DEVELOPING INDIVIDUAL, NOT ONLY THE IN UTERO EXPOSURE. THIS REVIEW EXAMINES THE GENETIC AND EPIGENETIC ALTERATIONS IN NUCLEAR AND MITOCHONDRIAL DNA ASSOCIATED WITH SMOKE EXPOSURE DURING THE MOST SENSITIVE PERIODS OF DEVELOPMENT (PRIOR TO CONCEPTION, PRENATAL AND EARLY POSTNATAL) AND ASSESSES HOW SUCH CHANGES MAY HAVE CONSEQUENCES FOR BOTH FETAL GROWTH AND DEVELOPMENT.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
15 2700  39 EXCESS IRON: CONSIDERATIONS RELATED TO DEVELOPMENT AND EARLY GROWTH. WHAT EFFECTS MIGHT ARISE FROM EARLY LIFE EXPOSURES TO HIGH IRON? THIS REVIEW CONSIDERS THE SPECIFIC EFFECTS OF HIGH IRON ON THE BRAIN, STEM CELLS, AND THE PROCESS OF ERYTHROPOIESIS AND IDENTIFIES GAPS IN OUR KNOWLEDGE OF WHAT MOLECULAR DAMAGE MAY BE INCURRED BY OXIDATIVE STRESS THAT IS IMPARTED BY HIGH IRON STATUS IN EARLY LIFE. SPECIFIC AREAS TO ENHANCE RESEARCH ON THIS TOPIC INCLUDE THE FOLLOWING: LONGITUDINAL BEHAVIORAL STUDIES OF CHILDREN TO TEST ASSOCIATIONS BETWEEN IRON EXPOSURES AND MOOD, EMOTION, COGNITION, AND MEMORY; ANIMAL STUDIES TO DETERMINE EPIGENETIC CHANGES THAT REPROGRAM BRAIN DEVELOPMENT AND METABOLIC CHANGES IN EARLY LIFE THAT COULD BE FOLLOWED THROUGH THE LIFE COURSE; AND THE ESTABLISHMENT OF HUMAN EPIGENETIC MARKERS OF IRON EXPOSURES AND OXIDATIVE STRESS THAT COULD BE MONITORED FOR EARLY ORIGINS OF ADULT CHRONIC DISEASES. IN ADDITION, EFFORTS TO UNDERSTAND HOW IRON EXPOSURE INFLUENCES STEM CELL BIOLOGY COULD BE ENHANCED BY ESTABLISHING PLATFORMS TO COLLECT BIOLOGICAL SPECIMENS, INCLUDING UMBILICAL CORD BLOOD AND AMNIOTIC FLUID, TO BE MADE AVAILABLE TO THE RESEARCH COMMUNITY. AT THE MOLECULAR LEVEL, THERE IS A NEED TO BETTER UNDERSTAND STRESS ERYTHROPOIESIS AND CHANGES IN IRON METABOLISM DURING PREGNANCY AND DEVELOPMENT, ESPECIALLY WITH RESPECT TO REGULATORY CONTROL UNDER HIGH IRON CONDITIONS THAT MIGHT PROMOTE INEFFECTIVE ERYTHROPOIESIS AND IRON-LOADING ANEMIA. THESE INVESTIGATIONS SHOULD FOCUS NOT ONLY ON FACTORS SUCH AS HEPCIDIN AND ERYTHROFERRONE BUT SHOULD ALSO INCLUDE NEWLY IDENTIFIED INTERACTIONS BETWEEN TRANSFERRIN RECEPTOR-2 AND THE ERYTHROPOIETIN RECEPTOR. FINALLY, DESPITE OUR UNDERSTANDING THAT SEVERAL KEY MICRONUTRIENTS (E.G., VITAMIN A, COPPER, MANGANESE, AND ZINC) SUPPORT IRON'S FUNCTION IN ERYTHROPOIESIS, HOW THESE NUTRIENTS INTERACT REMAINS, TO OUR KNOWLEDGE, UNKNOWN. IT IS NECESSARY TO CONSIDER MANY FACTORS WHEN FORMULATING RECOMMENDATIONS ON IRON SUPPLEMENTATION.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
16 1736  34 EARLY DETECTION AND PREVENTION OF SCHIZOPHRENIC PSYCHOSIS-A REVIEW. PSYCHOTIC DISORDERS OFTEN RUN A CHRONIC COURSE AND ARE ASSOCIATED WITH A CONSIDERABLE EMOTIONAL AND SOCIAL IMPACT FOR PATIENTS AND THEIR RELATIVES. THEREFORE, EARLY RECOGNITION, COMBINED WITH THE POSSIBILITY OF PREVENTIVE INTERVENTION, IS URGENTLY WARRANTED SINCE THE DURATION OF UNTREATED PSYCHOSIS (DUP) SIGNIFICANTLY DETERMINES THE FURTHER COURSE OF THE DISEASE. IN ADDITION TO ESTABLISHED DIAGNOSTIC TOOLS, NEUROBIOLOGICAL FACTORS IN THE DEVELOPMENT OF SCHIZOPHRENIC PSYCHOSES ARE INCREASINGLY BEING INVESTIGATED. IT IS SHOWN THAT NUMEROUS MOLECULAR ALTERATIONS ALREADY EXIST BEFORE THE CLINICAL ONSET OF THE DISEASE. AS SCHIZOPHRENIC PSYCHOSES ARE NOT ELICITED BY A SINGLE MUTATION IN THE DEOXYRIBONUCLEIC ACID (DNA) SEQUENCE, EPIGENETICS LIKELY CONSTITUTE THE MISSING LINK BETWEEN ENVIRONMENTAL INFLUENCES AND DISEASE DEVELOPMENT AND COULD POTENTIALLY SERVE AS A BIOMARKER. THE RESULTS FROM TRANSCRIPTOMIC AND PROTEOMIC STUDIES POINT TO A DYSREGULATED IMMUNE SYSTEM, LIKELY EVOKED BY EPIGENETIC ALTERATIONS. DESPITE THE INCREASING KNOWLEDGE OF THE NEUROBIOLOGICAL MECHANISMS INVOLVED IN THE DEVELOPMENT OF PSYCHOTIC DISORDERS, FURTHER RESEARCH EFFORTS WITH LARGE POPULATION-BASED STUDY DESIGNS ARE NEEDED TO IDENTIFY SUITABLE BIOMARKERS. IN CONCLUSION, A COMBINATION OF BLOOD EXAMINATIONS, FUNCTIONAL IMAGING TECHNIQUES, ELECTROENCEPHALOGRAPHY (EEG) INVESTIGATIONS AND POLYGENIC RISK SCORES SHOULD BE CONSIDERED AS THE BASIS FOR PREDICTING HOW SUBJECTS WILL TRANSITION INTO MANIFEST PSYCHOSIS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
17 6790  29 [DNA METHYLATION ANALYSIS IN ENVIRONMENTAL AND OCCUPATIONAL CANCER RESEARCH]. THE PRESENT PAPER REVIEWS RECENT LABORATORY METHODS AND EXPERIMENTAL EVIDENCE CONCERNING EPIGENETIC BIOMARKERS INVOLVED IN CARCINOGENESIS MECHANISMS. WE INTRODUCE DNA METHYLATION AND ITS ROLE IN GENE EXPRESSION CONTROL. DNA METHYLATION ANALYSIS MAY ALLOW TO IDENTIFY EARLY CHANGES LEADING TO CANCER AND OTHER CHRONIC DISEASES. WE DESCRIBE HERE STRATEGIES FOR LABORATORY ANALYSES AND THEIR POSSIBLE APPLICATIONS. WE EXAMINE RESULTS FROM RECENT EXPERIMENTAL STUDIES SUGGESTING THAT THE EFFECTS OF CERTAIN OCCUPATIONAL AGENTS ARE MEDIATED BY ALTERATIONS IN DNA METHYLATION. PLANNING AND CONDUCTING INVESTIGATIONS ON EXPOSED HUMAN SUBJECTS WILL ALLOW TO VERIFY WHETHER DNA METHYLATION CHANGES IDENTIFIED IN ANIMAL AND IN-VITRO STUDIES MAY BE USED AS EARLY-EFFECT AND SUSCEPTIBILITY BIOMARKERS. DNA METHYLATION ANALYSIS HAS THE POTENTIAL FOR FUTURE APPLICATIONS IN RISK ASSESSMENT AND PREVENTION PROGRAMS CONDUCTED ON SUBJECTS EXPOSED TO HUMAN CARCINOGENS.	2005	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
18 2918  30 GENE-ENVIRONMENT INTERACTIONS IN MAJOR MENTAL DISORDERS IN THE CZECH REPUBLIC. BACKGROUND: MENTAL DISORDERS AFFECT ABOUT ONE?-THIRD OF THE HUMAN POPULATION, ARE TYPICALLY CHRONIC AND SIGNIFICANTLY DECREASE THE QUALITY OF LIFE. PRESENTLY, THE TREATMENT OF MENTAL ILLNESSES IS FAR FROM ADEQUATE WITH A SUBSTANTIAL PROPORTION OF THE PATIENTS BEING PHARMACORESISTANT AND SUFFERING FROM RELAPSES. ONE OF THE REASONS FOR THIS COMPLICATED SITUATION IS THAT WE DO NOT PRECISELY KNOW ABOUT THE CAUSES OF MENTAL DISORDERS, SO THEIR TREATMENT CANNOT BE CAUSAL. THE ETIOLOGY OF A MENTAL DISORDER IS TYPICALLY BASED ON A COMBINATION OF MOLECULAR (GENETIC) AND ENVIRONMENTAL FACTORS. AIM: THE AIM OF THE PROJECT IS TO DISCOVER THE GENE-ENVIRONMENT INTERACTIONS (GXE) IN A WIDE SPECTRUM OF MENTAL DISORDERS. METHODS: THE DESIGN OF OUR STUDY IS INNOVATIVE IN THE SENSE THAT WE INTEND TO STUDY LARGE GROUPS OF ASSOCIATED MENTAL DISORDERS AS A WHOLE INSTEAD OF IN ISOLATION. THIS WOULD ENABLE US TO MAP OUT THE POSSIBLE ENVIRONMENTAL CAUSAL FACTORS IN DETAIL IN RELATION TO THEIR CHARACTER, MAGNITUDE AND TIMING. THE PROJECT ALSO ALLOWS A STUDY OF GENETICS (INCLUDING EPIGENETICS AND MICROBIOMES) AS WELL AS THE ENVIRONMENT SIMULTANEOUSLY. WE PLAN ON INVOLVING THREE STUDY GROUPS: THE FIRST GROUP ARE PATIENTS SUFFERING FROM SCHIZOPHRENIA OR A MOOD DISORDER SUCH AS MAJOR DEPRESSION, RECURRENT DEPRESSIVE DISORDER AND BIPOLAR AFFECTIVE DISORDER; THE SECOND GROUP OF PATIENTS HAVE ANXIETY DISORDERS; AND THE THIRD GROUP ARE HEALTHY VOLUNTEERS FROM THE GENERAL POPULATION WHO ARE GENETICALLY UNRELATED. ALL OF THE STUDY SUBJECTS WILL UNDERGO THE FOLLOWING ASSESSMENTS: A PSYCHIATRIC EXAMINATION, THE IDENTIFICATION OF STRESSFUL LIFE EVENTS WITH THE AID OF A QUESTIONNAIRE, THE EXAMINATION OF THEIR REACTION TO STRESS, GENETIC AND EPIGENETIC (MICRORNA) ASSESSMENTS AND THE ANALYSIS OF ORAL AND GUT MICROBIOME. CONCLUSION: WE EXPECT THAT SOME OF THE GENETIC AS WELL AS ENVIRONMENTAL FACTORS IN THE STUDIED MENTAL DISORDERS ARE SHARED, WHILE SOME OTHERS ARE SPECIFIC. WE ALSO EXPECT THAT THE GXE (GENE-ENVIRONMENT INTERACTION) IN SCHIZOPHRENIC AND AFFECTIVE DISORDERS WILL BE DIFFERENT FROM THE GXE IN ANXIETY DISORDERS AND THAT THE GXE IN THE STUDIED MENTAL DISORDERS WILL DIFFER GENERALLY FROM THE GXE IN HEALTHY VOLUNTEERS. OUR RESULTS CAN HELP IN THE PREVENTION AND INDIVIDUALIZED TREATMENT OF A RANGE OF MENTAL DISORDERS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
19  679  28 BRAIN FOODS - THE ROLE OF DIET IN BRAIN PERFORMANCE AND HEALTH. THE PERFORMANCE OF THE HUMAN BRAIN IS BASED ON AN INTERPLAY BETWEEN THE INHERITED GENOTYPE AND EXTERNAL ENVIRONMENTAL FACTORS, INCLUDING DIET. FOOD AND NUTRITION, ESSENTIAL IN MAINTENANCE OF BRAIN PERFORMANCE, ALSO AID IN PREVENTION AND TREATMENT OF MENTAL DISORDERS. BOTH THE OVERALL COMPOSITION OF THE HUMAN DIET AND SPECIFIC DIETARY COMPONENTS HAVE BEEN SHOWN TO HAVE AN IMPACT ON BRAIN FUNCTION IN VARIOUS EXPERIMENTAL MODELS AND EPIDEMIOLOGICAL STUDIES. THIS NARRATIVE REVIEW PROVIDES AN OVERVIEW OF THE ROLE OF DIET IN 5 KEY AREAS OF BRAIN FUNCTION RELATED TO MENTAL HEALTH AND PERFORMANCE, INCLUDING: (1) BRAIN DEVELOPMENT, (2) SIGNALING NETWORKS AND NEUROTRANSMITTERS IN THE BRAIN, (3) COGNITION AND MEMORY, (4) THE BALANCE BETWEEN PROTEIN FORMATION AND DEGRADATION, AND (5) DETERIORATIVE EFFECTS DUE TO CHRONIC INFLAMMATORY PROCESSES. FINALLY, THE ROLE OF DIET IN EPIGENETIC REGULATION OF BRAIN PHYSIOLOGY IS DISCUSSED.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
20 6876  40 [PROLONGED EXPOSURE TO ATMOSPHERIC AIR POLLUTION AND MORTALITY FROM RESPIRATORY CAUSES]. DIFFERENT DESIGNS CAN BE USED TO ANALYZE THE RELATIONSHIPS BETWEEN RESPIRATORY MORTALITY AND LONG TERM EXPOSURE TO ATMOSPHERIC POLLUTION: EPIDEMIOLOGICAL STUDIES (COHORT, PREVALENCE STUDY) DEMONSTRATE THE REALITY OF THE RELATIONSHIP AND TOXICOLOGICAL STUDIES EXPLAIN IT. COHORT STUDIES HAVE THE ADVANTAGE OF BEING ABLE TO TAKE INTO ACCOUNT MANY CONFOUNDING FACTORS AND THUS AVOID BIASES (WHICH IS NOT THE CASE WITH PREVALENCE STUDIES), BUT REQUIRE SIGNIFICANT HUMAN AND FINANCIAL RESOURCES. THEY WERE FIRST ADOPTED IN THE US, BUT ARE NOW MORE OFTEN APPLIED IN EUROPE. THE RESULTS ARE RELATIVELY CONSISTENT, AS THEY ALL SHOW A STATISTICALLY SIGNIFICANT ASSOCIATION BETWEEN AN INCREASE IN PARTICULATE POLLUTION AND CARDIOPULMONARY MORTALITY. MORTALITY FROM LUNG CANCER IS ALSO ASSOCIATED WITH LONG TERM EXPOSITION TO PARTICLES AND SOMETIMES TO OZONE OR NITROGEN OXIDES. CEREBROVASCULAR DISEASES AND SUDDEN DEATH OF YOUNG CHILDREN HAVE ALSO BEEN ASSOCIATED WITH PARTICULATE POLLUTION. THE RELATIONSHIPS ARE MORE POWERFUL FOR LONG TERM THAN SHORT TERM EXPOSURE BUT ARE ALSO LINEAR AND WITHOUT THRESHOLD. IN ORDER TO EXPLAIN THESE EFFECTS (TODAY THE CAUSALITY OF THE RELATIONSHIP IS CERTAIN) THERE ARE MANY POSSIBLE FACTORS, PARTICULARLY REGARDING PARTICULATE EXPOSURES: AN INCREASE IN CARDIOVASCULAR RISK BIOMARKERS (FIBRINOGEN, WHITE BLOOD CELLS, AND PLATELETS), ATHEROSCLEROSIS, CHRONIC INFLAMMATION OF LUNG TISSUES INCREASED BY ACUTE EXPOSURE, ETC. MORE AND MORE STUDIES ADDRESS THE INTERACTION BETWEEN GENE AND ENVIRONMENT AND EVEN EPIGENETIC PHENOMENA WHICH COULD BE RESPONSIBLE OF THESE EFFECTS. PUBLIC HEALTH IMPACT COULD BE QUANTIFIED. THE EUROPEAN E&H SURVEILLANCE PROGRAM APHEIS, FOR EXAMPLE, ESTIMATED THAT IF PM2.5 LEVELS REMAINED BELOW 15 MICROG/M(3), A 30 YEAR OLD PERSON COULD SEE HIS LIFE EXPECTANCY INCREASED BY 1 MONTH TO 2 YEARS, DEPENDING ON THE STUDIED CITY. FINALLY, MORTALITY IS NOT THE ONLY RELEVANT INDICATOR FOR HEALTH EFFECTS OF AIR POLLUTION. ISAAC STUDIES ADDRESS ASTHMA, ALLERGIC RHINITIS AND ECZEMA AMONG CHILDREN.	2009