1  1852 207 ELECTRONIC CIGARETTES: THEIR CONSTITUENTS AND POTENTIAL LINKS TO ASTHMA. PURPOSE OF REVIEW: VAPING IS GAINING POPULARITY IN THE USA, PARTICULARLY AMONG TEENS AND YOUNG ADULTS. WHILE E-CIGS ARE COMMONLY REPRESENTED AS SAFER ALTERNATIVES TO TOBACCO CIGARETTES, LITTLE IS KNOWN REGARDING THE HEALTH EFFECTS OF THEIR SHORT- OR LONG-TERM USE, ESPECIALLY IN INDIVIDUALS WITH PRE-EXISTING RESPIRATORY DISEASES SUCH AS ASTHMA. FLAVORED E-CIG LIQUIDS (E-LIQUIDS) AND E-CIG AEROSOLS CONTAIN AIRWAY IRRITANTS AND TOXICANTS THAT HAVE BEEN IMPLICATED IN THE PATHOGENESIS AND WORSENING OF LUNG DISEASES. IN THIS REVIEW, WE WILL SUMMARIZE EXISTING DATA ON POTENTIAL HEALTH EFFECTS OF COMPONENTS PRESENT IN E-CIG AEROSOLS, SUCH AS PROPYLENE GLYCOL, VEGETABLE GLYCERIN, NICOTINE, AND FLAVORINGS, AND DISCUSS THEIR RELEVANCE IN THE CONTEXT OF ASTHMA. RECENT FINDINGS: RECENT SURVEY DATA INDICATE THAT ADOLESCENTS WITH ASTHMA HAD A HIGHER PREVALENCE OF CURRENT E-CIG USE (12.4%) COMPARED TO THEIR NON-ASTHMATICS PEERS (10.2%) AND CONVEYED POSITIVE BELIEFS ABOUT TOBACCO PRODUCTS, ESPECIALLY E-CIGS. SIMILARLY, A STUDY CONDUCTED AMONG HIGH SCHOOL STUDENTS FROM ONTARIO, CANADA, INDICATED A GREATER LIKELIHOOD OF E-CIG USE IN ASTHMATICS AS COMPARED TO THEIR NON-ASTHMATIC PEERS. AVAILABILITY OF DIFFERENT FLAVORINGS IS OFTEN CITED AS THE MAIN REASON AMONG YOUTH/ADOLESCENTS FOR TRYING E-CIGS OR SWITCHING FROM CIGARETTES TO E-CIGS. OCCUPATIONAL INHALATION OF SOME COMMON FOOD-SAFE FLAVORING AGENTS IS REPORTED TO CAUSE OCCUPATIONAL ASTHMA AND WORSEN ASTHMATIC SYMPTOMS. MOREOVER, WORKPLACE INHALATION EXPOSURES TO THE FLAVORING AGENT DIACETYL HAVE CAUSED IRREVERSIBLE OBSTRUCTIVE AIRWAY DISEASE IN HEALTHY WORKERS. ADDITIONALLY, RECENT STUDIES REPORT THAT THERMAL DECOMPOSITION OF PROPYLENE GLYCOL (PG) AND VEGETABLE GLYCERIN (VG), THE BASE CONSTITUENTS OF E-LIQUIDS, PRODUCES REACTIVE CARBONYLS, INCLUDING ACROLEIN, FORMALDEHYDE, AND ACETALDEHYDE, WHICH HAVE KNOWN RESPIRATORY TOXICITIES. FURTHERMORE, RECENT NICOTINE STUDIES IN RODENTS REVEAL THAT PRENATAL NICOTINE EXPOSURES LEAD TO EPIGENETIC REPROGRAMMING IN THE OFFSPRING, ABNORMAL LUNG DEVELOPMENT, AND MULTIGENERATIONAL TRANSMISSION OF ASTHMATIC-LIKE SYMPTOMS. COMPARISONS OF THE TOXICITY AND HEALTH EFFECTS OF E-CIGS AND CONVENTIONAL CIGARETTES OFTEN FOCUS ON TOXICANTS KNOWN TO BE PRESENT IN CIGARETTE SMOKE (CS) (I.E., FORMALDEHYDE, NITROSAMINES, ETC.), AS WELL AS SMOKING-ASSOCIATED CLINICAL ENDPOINTS, SUCH AS CANCER, BRONCHITIS, AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). HOWEVER, THIS APPROACH DISREGARDS POTENTIAL TOXICITY OF COMPONENTS UNIQUE TO FLAVORED E-CIGS, SUCH AS PG, VG, AND THE MANY DIFFERENT FLAVORING CHEMICALS, WHICH LIKELY INDUCE RESPIRATORY EFFECTS NOT USUALLY OBSERVED IN CIGARETTE SMOKERS.	2017	

2  5380  57 RECENT UPDATES ON BIOMARKERS OF EXPOSURE AND SYSTEMIC TOXICITY IN E-CIGARETTE USERS AND EVALI. ELECTRONIC NICOTINE DELIVERY SYSTEMS (ENDS), OR E-CIGARETTES, ARE EMERGING TOBACCO PRODUCTS THAT PRODUCE AEROSOLS BY HEATING E-LIQUIDS, WHICH MOST OFTEN CONSIST OF PROPYLENE GLYCOL AND VEGETABLE GLYCERIN ALONG WITH VARIOUS FLAVORING COMPOUNDS, BYPASSING THE COMBUSTION THAT OCCURS IN THE USE OF TRADITIONAL TOBACCO CIGARETTES. THESE PRODUCTS HAVE SEEN A DRASTIC INCREASE IN POPULARITY IN RECENT YEARS BOTH AS SMOKING CESSATION DEVICES AS WELL AS AMONG YOUNGER GENERATIONS, DUE IN LARGE PART TO THE WIDESPREAD PERCEPTION AMONG CONSUMERS THAT E-CIGS ARE SIGNIFICANTLY LESS HARMFUL TO HEALTH THAN TRADITIONAL TOBACCO CIGARETTES. DUE TO THE NOVELTY OF ENDS AS WELL AS THEIR RAPIDLY INCREASING USE, RESEARCH INTO BIOMARKERS OF E-CIG EXPOSURE AND TOXICITY HAVE LAGGED BEHIND THEIR POPULARITY, LEAVING IMPORTANT QUESTIONS ABOUT THEIR POTENTIAL TOXICITY UNANSWERED. RESEARCH INTO POTENTIAL BIOMARKERS OF ACUTE AND CHRONIC E-CIG USE, AND E-CIGARETTE- OR VAPING-ASSOCIATED LUNG INJURY IS NECESSARY FOR INFORMING BOTH CLINICAL AND REGULATORY DECISION-MAKING. WE AIM TO PROVIDE AN UPDATED REVIEW OF RECENT RESEARCH INTO POTENTIAL CIRCULATING, GENOMIC, TRANSCRIPTOMIC, AND EPIGENETIC BIOMARKERS OF EXPOSURE TO AND TOXICITY OF E-CIGS. WE ADDITIONALLY HIGHLIGHT RESEARCH AREAS THAT WARRANT ADDITIONAL STUDY TO GAIN A BETTER UNDERSTANDING OF HEALTH RISKS ASSOCIATED WITH ENDS USE, AS WELL AS TO PROVIDE VALIDATION OF EXISTING DATA AND METHODS FOR MEASURING AND ANALYZING E-CIG-ASSOCIATED BIOMARKERS IN HUMAN AND ANIMAL BIOFLUIDS, TISSUES, AND CELLS. THIS REVIEW ALSO HIGHLIGHTS ONGOING EFFORTS WITHIN THE WNY CENTER FOR RESEARCH ON FLAVORED TOBACCO FOR RESEARCH INTO NOVEL BIOMARKERS IN EXTRACELLULAR VESICLES THAT MAY BE ASSOCIATED WITH SHORT- AND LONG-TERM ENDS USE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
3  2838  31 FORMALDEHYDE CARCINOGENICITY RESEARCH: 30 YEARS AND COUNTING FOR MODE OF ACTION, EPIDEMIOLOGY, AND CANCER RISK ASSESSMENT. FORMALDEHYDE IS A WIDELY USED HIGH PRODUCTION CHEMICAL THAT IS ALSO RELEASED AS A BYPRODUCT OF COMBUSTION, OFF-GASSING OF VARIOUS BUILDING PRODUCTS, AND AS A FIXATIVE FOR PATHOLOGISTS AND EMBALMERS. WHAT IS NOT OFTEN REALIZED IS THAT FORMALDEHYDE IS ALSO PRODUCED AS A NORMAL PHYSIOLOGIC CHEMICAL IN ALL LIVING CELLS. IN 1980, CHRONIC INHALATION OF HIGH CONCENTRATIONS OF FORMALDEHYDE WAS SHOWN TO BE CARCINOGENIC, INDUCING A HIGH INCIDENCE OF NASAL SQUAMOUS CELL CARCINOMAS IN RATS. SOME EPIDEMIOLOGIC STUDIES HAVE ALSO FOUND INCREASED NUMBERS OF NASOPHARYNGEAL CARCINOMA AND LEUKEMIA IN HUMANS EXPOSED TO FORMALDEHYDE THAT RESULTED IN FORMALDEHYDE BEING CONSIDERED A KNOWN HUMAN CARCINOGEN. THIS ARTICLE REVIEWS THE DATA FOR RODENT AND HUMAN CARCINOGENICITY, EARLY MODE OF ACTION STUDIES, MORE RECENT MOLECULAR STUDIES OF BOTH ENDOGENOUS AND EXOGENOUS DNA ADDUCTS, AND EPIGENETIC STUDIES. IT GOES ON TO DEMONSTRATE THE POWER OF THESE RESEARCH STUDIES TO PROVIDE CRITICAL DATA TO IMPROVE OUR ABILITY TO DEVELOP SCIENCE-BASED CANCER RISK ASSESSMENTS, INSTEAD OF DEFAULT APPROACHES. THE COMPLEXITY OF CONSTANT PHYSIOLOGIC EXPOSURE TO A KNOWN CARCINOGEN REQUIRES THAT NEW WAYS OF THINKING BE INCORPORATED INTO DETERMINATIONS OF CANCER RISK ASSESSMENT FOR FORMALDEHYDE, OTHER ENDOGENOUS CARCINOGENS, AND THE ROLE OF BACKGROUND ENDOGENOUS DNA DAMAGE AND MUTAGENESIS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
4  4529  29 MULTIGENERATIONAL GRAPHENE OXIDE INTOXICATION RESULTS IN REPRODUCTION DISORDERS AT THE MOLECULAR LEVEL OF VITELLOGENIN PROTEIN EXPRESSION IN ACHETA DOMESTICUS. THE ANTHROPOGENIC ACTIVITIES MAY LEAD TO ACCUMULATION OF GRAPHENE OXIDE (GO) POLLUTION IN THE ENVIRONMENT. ORGANISMS EXPOSED TO CHRONIC OR MULTIGENERATIONAL GO INTOXICATION CAN PRESENT REPRODUCTION DEPLETION. VITELLOGENIN (VG) HAS BEEN USED AS A PARAMETER FOR EVALUATING FEMALE FERTILITY DUE TO ITS IMPORTANCE IN EMBRYO NUTRITION. IN THIS STUDY, WE USED A PROMISING MODEL ORGANISM, ACHETA DOMESTICUS, WHICH WAS INTOXICATED WITH GO IN FOOD FOR THREE GENERATIONS. THE AIM OF THE STUDY WAS TO INVESTIGATE THE PROCESS OF VG SYNTHESIS IN CRICKETS DEPENDING ON THE EXPOSURE TIME, GO CONCENTRATION, AND AGE OF THE FEMALES. THE RESULTS REVEALED THAT CHRONIC GO INTOXICATION HAD ADVERSE EFFECTS ON THE VG EXPRESSION PATTERN. THE 1ST GENERATION OF INSECTS SHOWING LOW VG EXPRESSION WAS MOST AFFECTED. THE 2ND GENERATION OF A. DOMESTICUS PRESENTED A HIGH VG EXPRESSION. THE LAST INVESTIGATED GENERATION SEEMED TO COPE WITH STRESS CAUSED BY GO, AND THE VG EXPRESSION WAS BALANCED. WE SUGGEST THAT THE EPIGENETIC MECHANISMS MAY PLAY A ROLE IN THE INFORMATION TRANSFER TO THE NEXT GENERATIONS ON HOW TO REACT TO THE RISK FACTOR AND KEEP REPRODUCTION AT A HIGH RATE. WE SUSPECT THAT CHRONIC GO INTOXICATION CAN DISTURB THE REGULAR FORMATION OF THE VG QUATERNARY STRUCTURE, RESULTING IN CONSEQUENCES FOR DEVELOPING AN EMBRYO.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
5   747  27 CANNABIS-INDUCED HYPODOPAMINERGIC ANHEDONIA AND COGNITIVE DECLINE IN HUMANS: EMBRACING PUTATIVE INDUCTION OF DOPAMINE HOMEOSTASIS. OVER YEARS, THE REGULAR USE OF CANNABIS HAS SUBSTANTIALLY INCREASED AMONG YOUNG ADULTS, AS INDICATED BY THE RISE IN CANNABIS USE DISORDER (CUD), WITH AN ESTIMATED PREVALENCE OF 8. 3% IN THE UNITED STATES. RESEARCH SHOWS THAT EXPOSURE TO CANNABIS IS ASSOCIATED WITH HYPODOPAMINERGIC ANHEDONIA (DEPRESSION), COGNITIVE DECLINE, POOR MEMORY, INATTENTION, IMPAIRED LEARNING PERFORMANCE, REDUCED DOPAMINE BRAIN RESPONSE-ASSOCIATED EMOTIONALITY, AND INCREASED ADDICTION SEVERITY IN YOUNG ADULTS. THE ADDICTION MEDICINE COMMUNITY IS INCREASING CONCERN BECAUSE OF THE HIGH CONTENT OF DELTA-9-TETRAHYDROCANNABINOL (THC) CURRENTLY FOUND IN ORAL AND VAPING CANNABIS PRODUCTS, THE COGNITIVE EFFECTS OF CANNABIS MAY BECOME MORE PRONOUNCED IN YOUNG ADULTS WHO USE THESE CANNABIS PRODUCTS. PRELIMINARY RESEARCH SUGGESTS THAT IT IS POSSIBLE TO INDUCE 'DOPAMINE HOMEOSTASIS,' THAT IS, RESTORE DOPAMINE FUNCTION WITH DOPAMINE UPREGULATION WITH THE PROPOSED COMPOUND AND NORMALIZE BEHAVIOR IN CHRONIC CANNABIS USERS WITH CANNABIS-INDUCED HYPODOPAMINERGIC ANHEDONIA (DEPRESSION) AND COGNITIVE DECLINE. THIS PSYCHOLOGICAL, NEUROBIOLOGICAL, ANATOMICAL, GENETIC, AND EPIGENETIC RESEARCH ALSO COULD PROVIDE EVIDENCE TO USE FOR THE DEVELOPMENT OF AN APPROPRIATE POLICY REGARDING THE DECRIMINALIZATION OF CANNABIS FOR RECREATIONAL USE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
6  5174  41 PREDICTIVE AND PROGNOSTIC BIOMARKERS OF RESPIRATORY DISEASES DUE TO PARTICULATE MATTER EXPOSURE. AIR POLLUTION IS GETTING SEVERE AND CONCERNS ABOUT ITS TOXICITY EFFECTS ON AIRWAY AND LUNG DISEASE ARE ALSO INCREASING. PARTICULATE MATTER (PM) IS MAJOR COMPONENT OF AIR POLLUTANT. IT CAUSES RESPIRATORY DISEASES, SUCH AS ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, LUNG CANCER, AND SO ON. PM PARTICLES ENTER THE AIRWAY AND LUNG BY INHALATION, CAUSING DAMAGES TO THEM. ESPECIALLY, PM(2.5) CAN PENETRATE INTO THE ALVEOLUS AND PASS TO THE SYSTEMIC CIRCULATION. IT CAN AFFECT THE CARDIOPULMONARY SYSTEM AND CAUSE CARDIOPULMONARY DISORDERS. IN THIS REVIEW, WE FOCUSED ON PM-INDUCING TOXICITY MECHANISMS IN THE FRAMEWORK OF OXIDATIVE STRESS, INFLAMMATION, AND EPIGENETIC CHANGES. WE ALSO REVIEWED ITS CORRELATION WITH RESPIRATORY DISEASES. IN ADDITION, WE REVIEWED BIOMARKERS RELATED TO PM-INDUCED RESPIRATORY DISEASES. THESE BIOMARKERS MIGHT BE USED FOR DISEASE PREDICTION AND EARLY DIAGNOSIS. WITH RECENT TREND OF USING GENOMIC ANALYSIS TOOLS IN THE FIELD OF TOXICOGENOMICS, RESPIRATORY DISEASE BIOMARKERS ASSOCIATED WITH PM WILL BE CONTINUOUSLY INVESTIGATED. EFFECTIVE BIOMARKERS DERIVED FROM EARLIER STUDIES AND FURTHER STUDIES MIGHT BE UTILIZED TO REDUCE RESPIRATORY DISEASES.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
7   298  51 AIR POLLUTION AND AIRWAY DISEASE. EPIDEMIOLOGICAL AND TOXICOLOGICAL RESEARCH CONTINUES TO SUPPORT A LINK BETWEEN URBAN AIR POLLUTION AND AN INCREASED INCIDENCE AND/OR SEVERITY OF AIRWAY DISEASE. DETRIMENTAL EFFECTS OF OZONE (O(3)), NITROGEN DIOXIDE (NO(2)) AND PARTICULATE MATTER (PM), AS WELL AS TRAFFIC-RELATED POLLUTION AS A WHOLE, ON RESPIRATORY SYMPTOMS AND FUNCTION ARE WELL DOCUMENTED. NOT ONLY DO WE HAVE STRONG EPIDEMIOLOGICAL EVIDENCE OF A RELATIONSHIP BETWEEN AIR POLLUTION AND EXACERBATION OF ASTHMA AND RESPIRATORY MORBIDITY AND MORTALITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), BUT RECENT STUDIES, PARTICULARLY IN URBAN AREAS, HAVE SUGGESTED A ROLE FOR POLLUTANTS IN THE DEVELOPMENT OF BOTH ASTHMA AND COPD. SIMILARLY, WHILE PREVALENCE AND SEVERITY OF ATOPIC CONDITIONS APPEAR TO BE MORE COMMON IN URBAN COMPARED WITH RURAL COMMUNITIES, EVIDENCE IS EMERGING THAT TRAFFIC-RELATED POLLUTANTS MAY CONTRIBUTE TO THE DEVELOPMENT OF ALLERGY. FURTHERMORE, NUMEROUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST AN ASSOCIATION BETWEEN EXPOSURE TO NO(2) , O(3) , PM AND COMBUSTION PRODUCTS OF BIOMASS FUELS AND AN INCREASED SUSCEPTIBILITY TO AND MORBIDITY FROM RESPIRATORY INFECTION. GIVEN THE CONSIDERABLE CONTRIBUTION THAT TRAFFIC EMISSIONS MAKE TO URBAN AIR POLLUTION RESEARCHERS HAVE SOUGHT TO CHARACTERIZE THE RELATIVE TOXICITY OF TRAFFIC-RELATED PM POLLUTANTS. RECENT ADVANCES IN MECHANISMS IMPLICATED IN THE ASSOCIATION OF AIR POLLUTANTS AND AIRWAY DISEASE INCLUDE EPIGENETIC ALTERATION OF GENES BY COMBUSTION-RELATED POLLUTANTS AND HOW POLYMORPHISMS IN GENES INVOLVED IN ANTIOXIDANT PATHWAYS AND AIRWAY INFLAMMATION CAN MODIFY RESPONSES TO AIR POLLUTION EXPOSURES. OTHER INTERESTING EPIDEMIOLOGICAL OBSERVATIONS RELATED TO INCREASED HOST SUSCEPTIBILITY INCLUDE A POSSIBLE LINK BETWEEN CHRONIC PM EXPOSURE DURING CHILDHOOD AND VULNERABILITY TO COPD IN ADULTHOOD, AND THAT INFANTS SUBJECTED TO HIGHER PRENATAL LEVELS OF AIR POLLUTION MAY BE AT GREATER RISK OF DEVELOPING RESPIRATORY CONDITIONS. WHILE THE CHARACTERIZATION OF POLLUTANT COMPONENTS AND SOURCES PROMISE TO GUIDE POLLUTION CONTROL STRATEGIES, THE IDENTIFICATION OF SUSCEPTIBLE SUBPOPULATIONS WILL BE NECESSARY IF TARGETED THERAPY/PREVENTION OF POLLUTION-INDUCED RESPIRATORY DISEASES IS TO BE DEVELOPED.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
8   363  41 AMBIENT AIR POLLUTION: HEALTH HAZARDS TO CHILDREN. AMBIENT AIR POLLUTION IS PRODUCED BY SOURCES INCLUDING VEHICULAR TRAFFIC, COAL-FIRED POWER PLANTS, HYDRAULIC FRACTURING, AGRICULTURAL PRODUCTION, AND FOREST FIRES. IT CONSISTS OF PRIMARY POLLUTANTS GENERATED BY COMBUSTION AND SECONDARY POLLUTANTS FORMED IN THE ATMOSPHERE FROM PRECURSOR GASES. AIR POLLUTION CAUSES AND EXACERBATES CLIMATE CHANGE, AND CLIMATE CHANGE WORSENS HEALTH EFFECTS OF AIR POLLUTION. INFANTS AND CHILDREN ARE UNIQUELY SENSITIVE TO AIR POLLUTION, BECAUSE THEIR ORGANS ARE DEVELOPING AND THEY HAVE HIGHER AIR PER BODY WEIGHT INTAKE. HEALTH EFFECTS LINKED TO AIR POLLUTION INCLUDE NOT ONLY EXACERBATIONS OF RESPIRATORY DISEASES BUT ALSO REDUCED LUNG FUNCTION DEVELOPMENT AND INCREASED ASTHMA INCIDENCE. ADDITIONAL OUTCOMES OF CONCERN INCLUDE PRETERM BIRTH, LOW BIRTH WEIGHT, NEURODEVELOPMENTAL DISORDERS, IQ LOSS, PEDIATRIC CANCERS, AND INCREASED RISKS FOR ADULT CHRONIC DISEASES. THESE EFFECTS ARE MEDIATED BY OXIDATIVE STRESS, CHRONIC INFLAMMATION, ENDOCRINE DISRUPTION, AND GENETIC AND EPIGENETIC MECHANISMS ACROSS THE LIFE SPAN. NATURAL EXPERIMENTS DEMONSTRATE THAT WITH INITIATIVES SUCH AS INCREASED USE OF PUBLIC TRANSPORTATION, BOTH AIR QUALITY AND COMMUNITY HEALTH IMPROVE. SIMILARLY, THE CLEAN AIR ACT HAS IMPROVED AIR QUALITY, ALTHOUGH EXPOSURE INEQUITIES PERSIST. OTHER EFFECTIVE STRATEGIES FOR REDUCING AIR POLLUTION INCLUDE ENDING RELIANCE ON COAL, OIL, AND GAS; REGULATING INDUSTRIAL EMISSIONS; REDUCING EXPOSURE WITH ATTENTION TO PROXIMITY OF RESIDENCES, SCHOOLS, AND CHILD CARE FACILITIES TO TRAFFIC; AND A GREATER AWARENESS OF THE AIR QUALITY INDEX. THIS POLICY REVIEWS BOTH SHORT- AND LONG-TERM HEALTH CONSEQUENCES OF AMBIENT AIR POLLUTION, ESPECIALLY IN RELATION TO DEVELOPMENTAL EXPOSURES. IT EXAMINES INDIVIDUAL, COMMUNITY, AND LEGISLATIVE STRATEGIES TO MITIGATE AIR POLLUTION.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
9  6485  36 TOXICOLOGICAL MECHANISM OF INDIVIDUAL SUSCEPTIBILITY TO FORMALDEHYDE-INDUCED RESPIRATORY EFFECTS. UNDERSTANDING THE MECHANISMS OF INDIVIDUAL SUSCEPTIBILITY TO EXPOSURE TO ENVIRONMENTAL POLLUTANTS HAS BEEN A CHALLENGE IN HEALTH RISK ASSESSMENT. HERE, AN INTEGRATED APPROACH COMBINING A CRISPR SCREEN IN HUMAN CELLS AND EPIDEMIOLOGICAL ANALYSIS WAS DEVELOPED TO IDENTIFY THE INDIVIDUAL SUSCEPTIBILITY TO THE ADVERSE HEALTH EFFECTS OF AIR POLLUTANTS BY TAKING FORMALDEHYDE (FA) AND THE ASSOCIATED CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AS A CASE STUDY. AMONG THE PRIMARY HITS OF CRISPR SCREENING OF FA IN HUMAN A549 CELLS, HTR4 WAS THE ONLY GENE GENETICALLY ASSOCIATED WITH COPD SUSCEPTIBILITY IN GLOBAL POPULATIONS. HOWEVER, THE ASSOCIATION BETWEEN HTR4 AND FA-INDUCED RESPIRATORY TOXICITY IS UNKNOWN IN THE LITERATURE. ADVERSE OUTCOME PATHWAY (AOP) NETWORK ANALYSIS OF CRISPR SCREEN HITS PROVIDED A POTENTIAL MECHANISTIC LINK BETWEEN ACTIVATION OF HTR4 (MOLECULAR INITIATING EVENT) AND FA-INDUCED LUNG INJURY (ADVERSE OUTCOME). SYSTEMATIC TOXICOLOGY TESTS (IN VITRO AND ANIMAL EXPERIMENTS) WERE CONDUCTED TO REVEAL THE HTR4-INVOLVED BIOLOGICAL MECHANISMS UNDERLYING THE SUSCEPTIBILITY TO ADVERSE HEALTH EFFECTS OF FA. FUNCTIONALITY AND ENHANCED EXPRESSION OF HTR4 WERE REQUIRED FOR SUSCEPTIBILITY TO FA-INDUCED LUNG INJURY, AND FA-INDUCED EPIGENETIC CHANGES COULD RESULT IN ENHANCED EXPRESSION OF HTR4. SPECIFIC EPIGENETIC AND GENETIC CHARACTERISTICS OF HTR4 WERE ASSOCIATED WITH THE PROGRESSION AND PREVALENCE OF COPD, RESPECTIVELY, AND THESE GENETIC RISK FACTORS FOR COPD COULD BE POTENTIAL BIOMARKERS OF INDIVIDUAL SUSCEPTIBILITY TO ADVERSE RESPIRATORY EFFECTS OF FA. THESE BIOMARKERS COULD BE OF GREAT SIGNIFICANCE FOR DEFINING SUBPOPULATIONS SUSCEPTIBLE TO EXPOSURE TO FA AND REDUCING UNCERTAINTY IN THE NEXT-GENERATION HEALTH RISK ASSESSMENT OF AIR POLLUTANTS. OUR STUDY DELINEATED A NOVEL TOXICOLOGICAL PATHWAY MEDIATED BY HTR4 IN FA-INDUCED LUNG INJURY, WHICH COULD PROVIDE A MECHANISTIC UNDERSTANDING OF THE POTENTIAL BIOMARKERS OF INDIVIDUAL SUSCEPTIBILITY TO ADVERSE RESPIRATORY EFFECTS OF FA.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
10  5623  38 SECOND-HAND SMOKE AND HUMAN LUNG CANCER. SINCE THE EARLY 1980S, THERE HAS BEEN GROWING CONCERN ABOUT POTENTIAL HEALTH CONSEQUENCES OF EXPOSURE TO SECOND-HAND SMOKE (SHS). DESPITE SHS BEING ESTABLISHED AS A RISK FACTOR FOR LUNG CANCER DEVELOPMENT, THE ESTIMATED RISK HAS REMAINED SMALL YET SOMEHOW DEBATABLE. HUMAN EXPOSURE TO SHS IS COMPLICATED BECAUSE OF TEMPORAL VARIABILITIES IN SOURCE, COMPOSITION, AND CONCENTRATION OF SHS. THE TEMPORALITY OF EXPOSURE TO SHS IS IMPORTANT FOR HUMAN LUNG CARCINOGENESIS WITH A LATENCY OF MANY YEARS. TO EXPLORE THE CAUSAL EFFECT OF SHS IN LUNG CARCINOGENESIS, EXPOSURE ASSESSMENTS SHOULD ESTIMATE CHRONIC EXPOSURE TO SHS ON AN INDIVIDUAL BASIS. HOWEVER, CONVENTIONAL EXPOSURE ASSESSMENT FOR SHS RELIES ON ONE-OFF OR SHORT-TERM MEASUREMENTS OF SHS INDICES. A MORE RELIABLE APPROACH WOULD BE TO USE BIOLOGICAL MARKERS THAT ARE SPECIFIC FOR SHS EXPOSURE AND PERTINENT TO LUNG CANCER. THIS APPROACH REQUIRES AN UNDERSTANDING OF THE UNDERLYING MECHANISMS THROUGH WHICH SHS COULD CONTRIBUTE TO LUNG CARCINOGENESIS. THIS REVIEW IS A SYNOPSIS OF RESEARCH ON SHS AND LUNG CANCER, WITH SPECIAL FOCUS ON HYPOTHETICAL MODES OF ACTION OF SHS FOR CARCINOGENESIS, INCLUDING GENOTOXIC AND EPIGENETIC EFFECTS.	2008	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
11   734  34 CANCER HEALTHCARE DISPARITIES AMONG AFRICAN AMERICANS IN THE UNITED STATES. A NEED EXISTS TO EXAMINE RACIAL DISPARITIES IN THE HEALTHCARE ARENA AND THE IMPACT ON PATIENTS WITH CANCER. DESPITE ONGOING EFFORTS TO INCREASE EQUITY IN PRIMARY HEALTHCARE ACCESS, RACIAL AND SOCIOECONOMIC DISPARITIES PERSIST, THUS CONTRIBUTING TO DISPROPORTIONATE TREATMENT OUTCOMES AND SURVIVORSHIP AMONG MINORITY AND LOW-INCOME PATIENTS. SUCH DISPARITIES HAVE BEEN REVEALED IN TREATMENT COHORTS OF PATIENTS WITH MULTIPLE FORMS OF CANCER, INCLUDING BREAST, CERVICAL, OVARIAN, ENDOMETRIAL, PROSTATE, LUNG, COLORECTAL, GASTROINTESTINAL, AND HEPATOCELLULAR, AND HAVE BEEN ATTRIBUTED TO A RANGE OF CO-OCCURRING BEHAVIORAL, SOCIAL DETERMINANTS OF HEALTH, UNDERLYING GENETIC FACTORS, AS WELL AS ACCESS TO EDUCATIONAL OPPORTUNITIES THAT LIMIT THE QUALITY OF INFORMED HEALTHCARE. THESE VARIOUS INTERRELATED FACTORS WIDEN CANCER HEALTHCARE DISPARITIES SYNERGISTICALLY THROUGHOUT UNDERSERVED COMMUNITIES, AND THEIR INFLUENCE HAS BEEN AMPLIFIED BY THE CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC. FUNDAMENTALLY, A LACK OF BASIC AND CLINICAL RESEARCH EXISTS THAT FAILS TO ADEQUATELY REFLECT DIVERSITY AND MINORITY INVOLVEMENT IN DRUG DEVELOPMENT. ALTHOUGH OVERCOMING THE OBSTACLES RESPONSIBLE FOR CHRONIC TREATMENT DISPARITIES IS A FORMIDABLE TASK, PROMISING MEANS OF ACHIEVING MORE UNIFORM QUALITY HEALTHCARE ARE BECOMING MORE CLEARLY ELUCIDATED. TO REDUCE DISEASE PROGRESSION, INCREASE OVERALL SURVIVAL, AND IMPROVE THE HEALTH OF VULNERABLE POPULATIONS, IT IS NECESSARY TO IDENTIFY AND FULLY DISCLOSE ENVIRONMENTAL, BIOLOGICAL, AND ANCESTRAL FACTORS THAT IMPACT THE RISK FOR CANCER; HEAL HISTORICAL FRACTURES WITHIN COMMUNITIES; AND INCREASE PARTICIPATION OF RACIAL AND ETHNIC MINORITIES IN SCREENING EFFORTS AND RESEARCH STUDIES. THIS REQUIRES DEVELOPING A SYSTEM OF JUSTICE AND TRUST BASED ON SPECIFIC, SOLUTION-ORIENTED GRASSROOTS COMMUNITY EFFORTS WORKING IN TANDEM WITH MEDICAL AND PHARMACEUTICAL LEADERS. BY FULLY EXPLORING AND PINPOINTING THE UNDERLYING CAUSES OF HEALTHCARE DISPARITIES, IT SHOULD BE POSSIBLE TO DEFINE STRATEGIES AND INTERVENTIONS MOST LIKELY TO TRANSFORM CANCER CARE. THE ULTIMATE GOAL IS UNDERSTANDING INDIVIDUAL, CULTURAL, AND BIOLOGICAL VULNERABILITIES, INCLUDING ENVIRONMENTAL AND EPIGENETIC LIABILITIES, TO OPTIMIZE CANCER PREVENTION, DIAGNOSIS, AND TREATMENT.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                             
12  3901  40 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	
                                                                                                                                                                                                                                                                                                                                                                      
13   537  30 ASYMPTOMATIC HYPERURICEMIA: IS IT REALLY ASYMPTOMATIC? PURPOSE OF REVIEW: HYPERURICEMIA IS HIGHLY PREVALENT, AFFECTING APPROXIMATELY 38 MILLION INDIVIDUALS IN THE UNITED STATES. HOWEVER, THE SIGNIFICANCE OF ASYMPTOMATIC HYPERURICEMIA - HYPERURICEMIA IN THE ABSENCE OF GOUT - CONTINUES TO BE DEBATED. RECENT FINDINGS: ASYMPTOMATIC HYPERURICEMIA RESULTS IN MONOSODIUM URATE CRYSTAL DEPOSITION IN TISSUES, WHICH MAY PROMOTE CHRONIC INFLAMMATION. INTRACELLULARLY, HYPERURICEMIA INHIBITS THE MASTER REGULATOR ADENOSINE MONOPHOSPHATE (AMP)-ASSOCIATED PROTEIN KINASE AND MAY CONDITION INNATE IMMUNE RESPONSES THROUGH DURABLE EPIGENETIC MODIFICATIONS. AT THE POPULATION LEVEL, ASYMPTOMATIC HYPERURICEMIA IS ASSOCIATED WITH MULTIPLE COMORBIDITIES, INCLUDING HYPERTENSION, CHRONIC KIDNEY DISEASE, CORONARY ARTERY DISEASE, AND DIABETES; LIMITATIONS OF THESE STUDIES INCLUDE THAT MOST ARE RETROSPECTIVE AND SOME DO NOT RIGOROUSLY DISTINGUISH BETWEEN ASYMPTOMATIC HYPERURICEMIA AND GOUT. TREATMENT STUDIES SUGGEST THAT URATE LOWERING MAY REDUCE THE RISK OF INCIDENCE OR PROGRESSION OF SOME OF THESE COMORBIDITIES; UNFORTUNATELY, MANY OF THESE TREATMENT STUDIES ARE SMALL OR FLAWED, AND NOT ALL STUDY RESULTS ARE CONSISTENT. SUMMARY: ACCUMULATING EVIDENCE SUGGESTS THAT ASYMPTOMATIC HYPERURICEMIA CONTRIBUTES TO THE COMORBIDITIES WITH WHICH IT ASSOCIATES AND THAT PROPER ASYMPTOMATIC HYPERURICEMIA TREATMENT MAY REDUCE FUTURE RISK. ADDITIONAL PROSPECTIVE TRIALS ARE NEEDED TO DEFINITELY ESTABLISH CAUSALITY AND SUPPORT DECISION-MAKING AS TO WHETHER, AND WHICH PATIENTS WITH ASYMPTOMATIC HYPERURICEMIA WOULD WARRANT URATE-LOWERING TREATMENT.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
14  4910  26 PAIN EXPOSURE ASSOCIATES WITH TELOMERE LENGTH EROSION IN VERY PRETERM INFANTS. VERY PRETERM (VPT) INFANTS (GESTATIONAL AGE < 32 WEEKS) REQUIRE LONG-LASTING HOSPITALIZATION IN THE NEONATAL INTENSIVE CARE UNIT (NICU), EVEN IN ABSENCE OF SEVERE MORBIDITIES. DURING NICU STAY, LIFE-SAVING INTERVENTIONS OCCUR AND INCLUDE INVASIVE AND PAINFUL SKIN-BREAKING PROCEDURES (NICU-RELATED STRESS), WHICH CONSTITUTE A MAJOR EARLY ADVERSE EXPERIENCE FOR VPT INFANTS. TELOMERES ARE REPEAT-SEQUENCE AT THE END OF CHROMOSOMES, WHICH SHORTEN WITH AGE AND ARE HIGHLY SUSCEPTIBLE TO LIFE ADVERSITIES: THE EXPOSURE TO EARLY ADVERSE EXPERIENCES IS ASSOCIATED WITH SHORTER TELOMERE LENGTH (TL). NONETHELESS, PREVIOUS RESEARCH DID NOT ASSESS LONGITUDINALLY THE ASSOCIATION BETWEEN NICU-RELATED STRESS AND TL IN VPT INFANTS. IN THE PRESENT STUDY, LEUKOCYTE TL WAS ASSESSED FROM CORD BLOOD AT BIRTH IN 46 VPT INFANTS AND IN A GROUP OF 31 FULL-TERM (FT) INFANTS, AS WELL AS AT NICU DISCHARGE IN VPTS ONLY. NICU-RELATED STRESS WAS MEASURED AS THE NUMBER OF SKIN-BREAKING PROCEDURES OCCURRING THROUGHOUT THE NICU STAY. A SIGNIFICANT DIFFERENCE EMERGED FOR TL BETWEEN VPT INFANTS AND FT COUNTERPARTS AT BIRTH. TL DECREASED FROM BIRTH TO DISCHARGE IN VPT INFANTS, ALTHOUGH THE CHANGE WAS NOT SIGNIFICANT IN THE GROUP AS A WHOLE. THE AMOUNT OF NICU-RELATED STRESS EMERGED AS THE PRIMARY PREDICTOR OF TL EROSION IN VPT INFANTS, EVEN CONTROLLING FOR NEONATAL AND CLINICAL CONFOUNDERS. FURTHERMORE, VPT INFANTS EXPOSED TO HIGH NICU-RELATED STRESS EXHIBITED A MARKED AND SIGNIFICANT DECREASE IN TL, WHEREAS VPT EXPOSED TO LOW NICU-RELATED STRESS EXHIBITED A NON-SIGNIFICANT INCREASE. THE PRESENT STUDY CONFIRMS PREVIOUS EVIDENCE OF LONGER TELOMERES IN VPT INFANTS AT BIRTH COMPARED TO FT CONTROLS. MOREOVER, NICU-RELATED STRESS EMERGED AS A KEY REGULATOR OF TL EROSION FROM BIRTH TO DISCHARGE IN VPT INFANTS. FUTURE RESEARCH IS WARRANTED TO FURTHER EXPLORE TL EROSION IN VPT INFANTS AND THE FACTORS ASSOCIATED WITH INDIVIDUAL DIFFERENCES IN NICU-RELATED STRESS SUSCEPTIBILITY AT THE EPIGENETIC LEVEL.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
15  5961  35 TELOMERE LENGTH IN PRETERM INFANTS: A PROMISING BIOMARKER OF EARLY ADVERSITY AND CARE IN THE NEONATAL INTENSIVE CARE UNIT? PRETERM INFANTS PRESENT AN IMMATURE NEUROBEHAVIORAL PROFILE AT BIRTH, EVEN IN ABSENCE OF SEVERE BRAIN INJURIES AND PERINATAL COMPLICATIONS. AS SUCH, THEY REQUIRE A LONG-LASTING HOSPITALIZATION IN THE NEONATAL INTENSIVE CARE UNIT (NICU), WHICH IS THOUGHT TO GRANT AT-RISK NEWBORNS' SURVIVAL, BUT STILL ENTAILS A NUMBER OF PHYSICAL, PAINFUL, AND SOCIO-EMOTIONAL STRESSORS. HENCE, PRETERM BIRTH AND NICU STAY REPRESENT AN EARLY ADVERSE EXPERIENCE, WHICH HAS BEEN LINKED TO DETRIMENTAL CONSEQUENCES FOR NEUROLOGICAL, NEURO-ENDOCRINAL, BEHAVIORAL, AND SOCIO-EMOTIONAL DEVELOPMENT, AS WELL AS TO DISEASE LATER IN LIFE. RECENT ADVANCES IN THE BEHAVIORAL EPIGENETIC FIELD ARE HELPING US TO UNVEIL THE POTENTIAL MECHANISMS THROUGH WHICH EARLY NICU-RELATED STRESS MAY LEAD TO NEGATIVE DEVELOPMENTAL OUTCOMES. FROM THIS PERSPECTIVE, TELOMERE REGULATION MIGHT BE A KEY PROGRAMMING MECHANISM. TELOMERES ARE THE TERMINAL PORTION OF CHROMOSOMES AND ARE KNOWN TO GET SHORTER WITH AGE. MOREOVER, TELOMERE LENGTH (TL) IS AFFECTED BY THE EXPOSURE TO STRESS DURING EARLY DEVELOPMENT. AS SUCH, TL MIGHT BE AN INNOVATIVE BIOMARKER OF EARLY ADVERSE EXPOSURES IN YOUNG INFANTS AND CHILDREN. UNFORTUNATELY, THERE IS PAUCITY OF STUDIES INVESTIGATING TL IN POPULATIONS OF PRETERM INFANTS AND ITS ASSOCIATION WITH KNOWN NICU-RELATED STRESSORS REMAINS UNEXPLORED. IN THE PRESENT PAPER, THE POTENTIAL RELEVANCE OF TL FOR RESEARCH AND CLINICAL WORK WITH PRETERM INFANTS WILL BE UNDERLINED IN THE LIGHT OF RECENT CONTRIBUTIONS LINKING PROGRESSIVE TELOMERE SHORTENING AND EARLY EXPOSURE TO ADVERSE EXPERIENCES AND STRESSFUL ENVIRONMENTS IN HUMANS. FINALLY, INSIGHTS WILL BE PROVIDED TO GUIDE CLINICALLY RELEVANT TRANSLATIONAL RESEARCH ON TL IN THE FIELD OF VPT BIRTH AND NICU STAY.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
16  3630  38 INCLUSION OF SOCIAL AND STRUCTURAL DETERMINANTS OF HEALTH TO ADVANCE UNDERSTANDING OF THEIR INFLUENCE ON THE BIOLOGY OF CHRONIC DISEASE. SOCIAL DETERMINANTS OF HEALTH (SDOH) CONSIDER SOCIAL, POLITICAL, AND ECONOMIC FACTORS THAT CONTRIBUTE TO HEALTH DISPARITIES IN PATIENTS AND POPULATIONS. THE MOST COMMON HEALTH-RELATED SDOH EXPOSURES ARE FOOD AND HOUSING INSECURITY, FINANCIAL INSTABILITY, TRANSPORTATION NEEDS, LOW LEVELS OF EDUCATION, AND PSYCHOSOCIAL STRESS. THESE DOMAINS DESCRIBE RISKS THAT CAN IMPACT HEALTH OUTCOMES MORE THAN HEALTH CARE. EPIDEMIOLOGIC AND TRANSLATIONAL RESEARCH DEMONSTRATES THAT SDOH FACTORS REPRESENT EXPOSURES THAT PREDICT HARM AND IMPACT THE HEALTH OF INDIVIDUALS. INTERNATIONAL AND NATIONAL GUIDELINES URGE HEALTH PROFESSIONALS TO ADDRESS SDOH IN CLINICAL PRACTICE AND PUBLIC HEALTH. THE FURTHER IMPLEMENTATION OF THESE RECOMMENDATIONS INTO BASIC AND TRANSLATIONAL RESEARCH, HOWEVER, IS LAGGING. HEREIN, WE CONSIDER A PRECISION HEALTH FRAMEWORK TO DESCRIBE HOW SDOH CONTRIBUTES TO THE EXPOSOME AND EXACERBATES PHYSIOLOGIC PATHWAYS THAT LEAD TO CHRONIC DISEASE. SDOH FACTORS ARE ASSOCIATED WITH VARIOUS FORMS OF STRESSORS THAT IMPACT PHYSIOLOGICAL PROCESSES THROUGH EPIGENETIC, INFLAMMATORY, AND REDOX REGULATION. MANY SDOH EXPOSURES MAY ADD TO OR POTENTIATE THE PATHOLOGIC EFFECTS OF ADDITIONAL ENVIRONMENTAL EXPOSURES. THIS OVERVIEW AIMS TO INFORM BASIC LIFE SCIENCE AND TRANSLATIONAL RESEARCHERS ABOUT SDOH EXPOSURES THAT CAN CONFOUND ASSOCIATIONS BETWEEN CLASSIC BIOMEDICAL DETERMINANTS OF DISEASE AND HEALTH OUTCOMES. TO ADVANCE THE STUDY OF TOXICOLOGY THROUGH EITHER QUALITATIVE OR QUANTITATIVE ASSESSMENT OF EXPOSURES TO CHEMICAL AND BIOLOGICAL SUBSTANCES, A MORE COMPLETE ENVIRONMENTAL EVALUATION SHOULD INCLUDE SDOH EXPOSURES. WE DISCUSS COMMON APPROACHES TO MEASURE SDOH FACTORS AT INDIVIDUAL AND POPULATION LEVELS AND REVIEW THE ASSOCIATIONS BETWEEN SDOH RISK FACTORS AND PHYSIOLOGIC MECHANISMS THAT INFLUENCE CHRONIC DISEASE. WE PROVIDE CLINICAL AND POLICY-BASED MOTIVATION TO ENCOURAGE RESEARCHERS TO CONSIDER THE IMPACT OF SDOH EXPOSURES ON STUDY RESULTS AND DATA INTERPRETATION. WITH VALID MEASURES OF SDOH FACTORS INCORPORATED INTO STUDY DESIGN AND ANALYSES, FUTURE TOXICOLOGICAL RESEARCH MAY CONTRIBUTE TO AN EVIDENCE BASE THAT CAN BETTER INFORM PREVENTION AND TREATMENT OPTIONS, TO IMPROVE EQUITABLE CLINICAL CARE AND POPULATION HEALTH. (C) 2022 WILEY PERIODICALS LLC.	2022	
                                                                                                                                                                                                                                                                                                                                                    
17  2605  28 EPIGENETICS-A POTENTIAL MEDIATOR BETWEEN AIR POLLUTION AND PRETERM BIRTH. PRETERM BIRTH IS A MAJOR CAUSE OF INFANT MORBIDITY AND MORTALITY AND A POTENTIAL RISK FACTOR FOR ADULT CHRONIC DISEASE. WITH OVER 15 MILLION INFANTS BORN PRETERM WORLDWIDE EACH YEAR, PRETERM BIRTH POSES A GLOBAL HEALTH CONCERN. THERE IS A POSSIBLE ASSOCIATION BETWEEN AIR POLLUTION AND PRETERM BIRTH, THOUGH STUDIES HAVE BEEN INCONSISTENT, LIKELY DUE TO VARIATION IN STUDY DESIGN. HOW AIR POLLUTION INDUCES HEALTH EFFECTS IS UNCERTAIN; HOWEVER, STUDIES HAVE REPEATEDLY DEMONSTRATED THE EFFECTS OF AIR POLLUTION ON EPIGENETIC MODIFICATIONS. MORE RECENT EVIDENCE SUGGESTS THAT EPIGENETICS MAY, IN TURN, BE LINKED TO PRETERM BIRTH. DISCOVERY OF ENVIRONMENTALLY MODIFIABLE EPIGENETIC PROCESSES CONNECTED TO PRETERM BIRTH MAY HELP TO IDENTIFY WOMEN AT RISK OF PRETERM BIRTH, AND ULTIMATELY LEAD TO DEVELOPMENT OF NEW PRETERM BIRTH PREVENTION MEASURES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
18   107  40 A REVIEW OF PRE-CLINICAL MODELS FOR GULF WAR ILLNESS. GULF WAR ILLNESS (GWI) IS A CHRONIC MULTISYMPTOMATIC DISORDER THAT AFFLICTS OVER 1/3RD OF THE 1991 GW VETERANS. IT SPANS MULTIPLE BODILY SYSTEMS AND PRESENTS ITSELF AS A SYNDROME EXHIBITING DIVERSE SYMPTOMS INCLUDING FATIGUE, DEPRESSION, MOOD, AND MEMORY AND CONCENTRATION DEFICITS, MUSCULOSKELETAL PAIN AND GASTROINTESTINAL DISTRESS IN GW VETERANS. THE ETIOLOGY OF GWI IS COMPLEX AND MANY FACTORS, INCLUDING CHEMICAL, PHYSIOLOGICAL, AND ENVIRONMENTAL STRESSORS PRESENT IN THE GW ARENA, HAVE BEEN IMPLICATED FOR ITS DEVELOPMENT. IT HAS BEEN OVER 30 YEARS SINCE THE END OF THE GW BUT, GWI HAS BEEN PERSISTENT IN SUFFERING VETERANS WHO ARE ALSO DEALING WITH PAUCITY OF EFFECTIVE TREATMENTS. THE MULTIFACTORIAL ASPECT OF GWI ALONG WITH GENETIC HETEROGENEITY AND LACK OF AVAILABLE DATA SURROUNDING WAR-TIME EXPOSURES HAVE PROVED TO BE CHALLENGING IN DEVELOPING PRE-CLINICAL MODELS OF GWI. DESPITE THIS, OVER A DOZEN GWI ANIMAL MODELS EXIST IN THE LITERATURE. IN THIS ARTICLE, FOLLOWING A BRIEF DISCUSSION OF GW HISTORY, GWI DEFINITIONS, AND PROBABLE CAUSES FOR ITS PATHOGENESIS, WE WILL EXPAND UPON VARIOUS EXPERIMENTAL MODELS USED IN GWI LABORATORY RESEARCH. THESE ANIMAL MODELS WILL BE DISCUSSED IN THE CONTEXT OF THEIR ATTEMPTS AT MIMICKING GW-RELATED EXPOSURES WITH REGARDS TO THE VARIATIONS IN CHEMICAL COMBINATIONS, DOSES, AND FREQUENCY OF EXPOSURES. WE WILL DISCUSS THEIR ADVANTAGES AND LIMITATIONS IN MODELING GWI FOLLOWED BY A DISCUSSION OF BEHAVIORAL AND MOLECULAR FINDINGS IN THESE MODELS. THE MECHANISTIC DATA OBTAINED FROM THESE PRECLINICAL STUDIES HAVE OFFERED MULTIPLE MOLECULAR PATHWAYS INCLUDING CHRONIC INFLAMMATION, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, LIPID DISTURBANCES, CALCIUM HOMEOSTATIC ALTERATIONS, CHANGES IN GUT MICROBIOTA, AND EPIGENETIC MODIFICATIONS, AMONGST OTHERS FOR EXPLAINING GWI DEVELOPMENT AND ITS PERSISTENCE. FINALLY, THESE FINDINGS HAVE ALSO INFORMED US ON NOVEL DRUGGABLE TARGETS IN GWI. WHILE, IT HAS BEEN DIFFICULT TO CONCEIVE A SINGLE PRE-CLINICAL MODEL THAT COULD EXPRESS ALL THE GWI SIGNS AND EXHIBIT BIOLOGICAL COMPLEXITY REFLECTIVE OF THE CLINICAL PRESENTATION IN GWI, ANIMAL MODELS HAVE BEEN CRITICAL FOR IDENTIFYING MOLECULAR UNDERPINNINGS OF GWI AND EVALUATING TREATMENT STRATEGIES FOR GWI.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
19  4701  37 NICOTINE AND THE ADOLESCENT BRAIN. ADOLESCENCE ENCOMPASSES A SENSITIVE DEVELOPMENTAL PERIOD OF ENHANCED CLINICAL VULNERABILITY TO NICOTINE, TOBACCO, AND E-CIGARETTES. WHILE THERE ARE SOCIOCULTURAL INFLUENCES, DATA AT PRECLINICAL AND CLINICAL LEVELS INDICATE THAT THIS ADOLESCENT SENSITIVITY HAS STRONG NEUROBIOLOGICAL UNDERPINNINGS. ALTHOUGH DEFINITIONS OF ADOLESCENCE VARY, THE HALLMARK OF THIS PERIOD IS A PROFOUND REORGANIZATION OF BRAIN REGIONS NECESSARY FOR MATURE COGNITIVE AND EXECUTIVE FUNCTION, WORKING MEMORY, REWARD PROCESSING, EMOTIONAL REGULATION, AND MOTIVATED BEHAVIOR. REGULATING CRITICAL FACETS OF BRAIN MATURATION ARE NICOTINIC ACETYLCHOLINE RECEPTORS (NACHRS). HOWEVER, PERTURBATIONS OF CHOLINERGIC SYSTEMS DURING THIS TIME WITH NICOTINE, VIA TOBACCO OR E-CIGARETTES, HAVE UNIQUE CONSEQUENCES ON ADOLESCENT DEVELOPMENT. IN THIS REVIEW, WE HIGHLIGHT RECENT CLINICAL AND PRECLINICAL DATA EXAMINING THE ADOLESCENT BRAIN'S DISTINCT NEUROBIOLOGY AND UNIQUE SENSITIVITY TO NICOTINE. FIRST, WE DISCUSS WHAT DEFINES ADOLESCENCE BEFORE REVIEWING NORMATIVE STRUCTURAL AND NEUROCHEMICAL ALTERATIONS THAT PERSIST UNTIL EARLY ADULTHOOD, WITH AN EMPHASIS ON DOPAMINERGIC SYSTEMS. WE REVIEW HOW ACUTE EXPOSURE TO NICOTINE IMPACTS BRAIN DEVELOPMENT AND HOW DRUG RESPONSES DIFFER FROM THOSE SEEN IN ADULTS. FINALLY, WE DISCUSS THE PERSISTENT ALTERATIONS IN NEURONAL SIGNALING AND COGNITIVE FUNCTION THAT RESULT FROM CHRONIC NICOTINE EXPOSURE, WHILE HIGHLIGHTING A LOW DOSE, SEMI-CHRONIC EXPOSURE PARADIGM THAT MAY BETTER MODEL ADOLESCENT TOBACCO USE. WE ARGUE THAT NICOTINE EXPOSURE, INCREASINGLY OCCURRING AS A RESULT OF E-CIGARETTE USE, MAY INDUCE EPIGENETIC CHANGES THAT SENSITIZE THE BRAIN TO OTHER DRUGS AND PRIME IT FOR FUTURE SUBSTANCE ABUSE.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
20  4135  42 MECHANISMS OF LUNG DAMAGE AND DEVELOPMENT OF COPD DUE TO HOUSEHOLD BIOMASS-SMOKE EXPOSURE: INFLAMMATION, OXIDATIVE STRESS, MICRORNAS, AND GENE POLYMORPHISMS. CHRONIC EXPOSURE TO INDOOR BIOMASS SMOKE FROM THE COMBUSTION OF SOLID ORGANIC FUELS IS A MAJOR CAUSE OF DISEASE BURDEN WORLDWIDE. ALMOST 3 BILLION PEOPLE USE SOLID FUELS SUCH AS WOOD, CHARCOAL, AND CROP RESIDUES FOR INDOOR COOKING AND HEATING, ACCOUNTING FOR APPROXIMATELY 50% OF ALL HOUSEHOLDS AND 90% OF RURAL HOUSEHOLDS GLOBALLY. BIOMASS SMOKE CONTAINS MANY HAZARDOUS POLLUTANTS, RESULTING IN HOUSEHOLD AIR POLLUTION (HAP) EXPOSURE THAT OFTEN EXCEEDS INTERNATIONAL STANDARDS. LONG-TERM BIOMASS-SMOKE EXPOSURE IS ASSOCIATED WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IN ADULTS, A LEADING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE, CHRONIC BRONCHITIS, AND OTHER LUNG CONDITIONS. BIOMASS SMOKE-ASSOCIATED COPD DIFFERS FROM THE BEST-KNOWN CIGARETTE SMOKE-INDUCED COPD IN SEVERAL ASPECTS, SUCH AS A SLOWER DECLINE IN LUNG FUNCTION, GREATER AIRWAY INVOLVEMENT, AND LESS EMPHYSEMA, WHICH SUGGESTS A DIFFERENT PHENOTYPE AND PATHOPHYSIOLOGY. DESPITE THE HIGH BURDEN OF BIOMASS-ASSOCIATED COPD, THE MOLECULAR, GENETIC, AND EPIGENETIC MECHANISMS UNDERLYING ITS PATHOGENESIS ARE POORLY UNDERSTOOD. THIS REVIEW DESCRIBES THE PATHOGENIC MECHANISMS POTENTIALLY INVOLVED IN LUNG DAMAGE, THE DEVELOPMENT OF COPD ASSOCIATED WITH WOOD-DERIVED SMOKE EXPOSURE, AND THE INFLUENCE OF GENETIC AND EPIGENETIC FACTORS ON THE DEVELOPMENT OF THIS DISEASE.	2022