1 6392 97 THE ROLE OF THE GUT MICROBIOTA IN SCHIZOPHRENIA: CURRENT AND FUTURE PERSPECTIVES. OBJECTIVES: SCHIZOPHRENIA IS A POORLY UNDERSTOOD CHRONIC DISEASE. ITS PATHOPHYSIOLOGY IS COMPLEX, DYNAMIC, AND LINKED TO EPIGENETIC MECHANISMS AND MICROBIOTA INVOLVEMENT. NOWADAYS, CORRELATING SCHIZOPHRENIA WITH THE ENVIRONMENT MAKES SENSE OWING TO ITS MULTIDIMENSIONAL IMPLICATIONS: TEMPORAL AND SPATIAL VARIABILITY. MICROBIOTA INVOLVEMENT AND EPIGENETIC MECHANISMS ARE FACTORS THAT ARE CURRENTLY BEING CONSIDERED TO BETTER UNDERSTAND ANOTHER DIMENSION OF SCHIZOPHRENIA. METHODS: THIS REVIEW SUMMARISES AND DISCUSSES CURRENTLY AVAILABLE INFORMATION, FOCUSSING ON THE MICROBIOTA, EPIGENETIC MECHANISMS, TECHNOLOGICAL APPROACHES AIMED AT PERFORMING EXHAUSTIVE ANALYSES OF THE MICROBIOTA, AND PSYCHOTHERAPIES, TO ESTABLISH FUTURE PERSPECTIVES. RESULTS: THE CONNECTION BETWEEN THE MICROBIOTA, EPIGENETIC MECHANISMS AND TECHNOLOGICAL DEVELOPMENTS ALLOWS FOR FORMULATING NEW APPROACHES OBJECTIVELY ORIENTED TOWARDS THE DEVELOPMENT OF ALTERNATIVE PSYCHOTHERAPIES THAT MAY HELP TREAT SCHIZOPHRENIA. CONCLUSIONS: IN THIS REVIEW, THE GUT MICROBIOTA AND EPIGENETIC MECHANISMS WERE CONSIDERED AS KEY REGULATORS, REVEALING A POTENTIAL NEW AETIOLOGY OF SCHIZOPHRENIA. LIKEWISE, CONTINUOUS TECHNOLOGICAL ADVANCES (E.G. CULTUROMICS), AIMED AT THE MICROBIOTA-GUT-BRAIN AXIS GENERATE NEW EVIDENCE ON THIS CONCEPT. 2018 2 1736 30 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 3 3283 34 HIDDEN ROLE OF GUT MICROBIOME DYSBIOSIS IN SCHIZOPHRENIA: ANTIPSYCHOTICS OR PSYCHOBIOTICS AS THERAPEUTICS? SCHIZOPHRENIA IS A CHRONIC, HETEROGENEOUS NEURODEVELOPMENTAL DISORDER THAT HAS COMPLEX SYMPTOMS AND UNCERTAIN ETIOLOGY. MOUNTING EVIDENCE INDICATES THE INVOLVEMENT OF GENETICS AND EPIGENETIC DISTURBANCES, ALTERATION IN GUT MICROBIOME, IMMUNE SYSTEM ABNORMALITIES, AND ENVIRONMENTAL INFLUENCE IN THE DISEASE, BUT A SINGLE ROOT CAUSE AND MECHANISM INVOLVED HAS YET TO BE CONCLUSIVELY DETERMINED. CONSEQUENTLY, THE IDENTIFICATION OF DIAGNOSTIC MARKERS AND THE DEVELOPMENT OF PSYCHOTIC DRUGS FOR THE TREATMENT OF SCHIZOPHRENIA FACES A HIGH FAILURE RATE. THIS ARTICLE SURVEYS THE ETIOLOGY OF SCHIZOPHRENIA WITH A PARTICULAR FOCUS ON GUT MICROBIOTA REGULATION AND THE MICROBIAL SIGNALING SYSTEM THAT CORRELATES WITH THE BRAIN THROUGH THE VAGUS NERVE, ENTERIC NERVOUS SYSTEM, IMMUNE SYSTEM, AND PRODUCTION OF POSTBIOTICS. GUT MICROBIALLY PRODUCED MOLECULES MAY LAY THE GROUNDWORK FOR FURTHER INVESTIGATIONS INTO THE ROLE OF GUT MICROBIOTA DYSBIOSIS AND THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA. CURRENT TREATMENT OF SCHIZOPHRENIA IS LIMITED TO PSYCHOTHERAPY AND ANTIPSYCHOTIC DRUGS THAT HAVE SIGNIFICANT SIDE EFFECTS. THEREFORE, ALTERNATIVE THERAPEUTIC OPTIONS MERIT EXPLORATION. THE USE OF PSYCHOBIOTICS ALONE OR IN COMBINATION WITH ANTIPSYCHOTICS MAY PROMOTE THE DEVELOPMENT OF NOVEL THERAPEUTIC STRATEGIES. IN VIEW OF THE INDIVIDUAL GUT MICROBIOME STRUCTURE AND PERSONALIZED RESPONSE TO ANTIPSYCHOTIC DRUGS, A TAILORED AND TARGETED MANIPULATION OF GUT MICROBIAL DIVERSITY NATURALLY BY NOVEL PREBIOTICS (NON-DIGESTIBLE FIBER) MAY BE A SUCCESSFUL ALTERNATIVE THERAPEUTIC FOR THE TREATMENT OF SCHIZOPHRENIA PATIENTS. 2021 4 2526 29 EPIGENETICS APPLIED TO PSYCHIATRY: CLINICAL OPPORTUNITIES AND FUTURE CHALLENGES. PSYCHIATRIC DISORDERS ARE CLINICALLY HETEROGENEOUS AND DEBILITATING CHRONIC DISEASES RESULTING FROM A COMPLEX INTERPLAY BETWEEN GENE VARIANTS AND ENVIRONMENTAL FACTORS. EPIGENETIC PROCESSES, SUCH AS DNA METHYLATION AND HISTONE POSTTRANSLATIONAL MODIFICATIONS, INSTRUCT THE CELL/TISSUE TO CORRECTLY INTERPRET EXTERNAL SIGNALS AND ADJUST ITS FUNCTIONS ACCORDINGLY. GIVEN THAT EPIGENETIC MODIFICATIONS ARE SENSITIVE TO ENVIRONMENT, STABLE, AND REVERSIBLE, EPIGENETIC STUDIES IN PSYCHIATRY COULD REPRESENT A PROMISING APPROACH TO BETTER UNDERSTANDING AND TREATING DISEASE. IN THE PRESENT REVIEW, WE AIM TO DISCUSS THE CLINICAL OPPORTUNITIES AND CHALLENGES ARISING FROM THE EPIGENETIC RESEARCH IN PSYCHIATRY. USING SELECTED EXAMPLES, WE FIRST RECAPITULATE KEY FINDINGS SUPPORTING THE ROLE OF ADVERSE LIFE EVENTS, ALONE OR IN COMBINATION WITH GENETIC RISK, IN EPIGENETIC PROGRAMMING OF NEUROPSYCHIATRIC SYSTEMS. EPIGENETIC STUDIES FURTHER REPORT ENCOURAGING FINDINGS ABOUT THE USE OF METHYLATION CHANGES AS DIAGNOSTIC MARKERS OF DISEASE PHENOTYPE AND PREDICTIVE TOOLS OF PROGRESSION AND RESPONSE TO TREATMENT. THEN WE DISCUSS THE POTENTIAL OF USING TARGETED EPIGENETIC PHARMACOTHERAPY, COMBINED WITH PSYCHOSOCIAL INTERVENTIONS, FOR FUTURE PERSONALIZED MEDICINE FOR PATIENTS. FINALLY, WE REVIEW THE METHODOLOGICAL LIMITATIONS THAT COULD HINDER INTERPRETATION OF EPIGENETIC DATA IN PSYCHIATRY. THEY MAINLY ARISE FROM HETEROGENEITY AT THE INDIVIDUAL AND TISSUE LEVEL AND REQUIRE FUTURE STRATEGIES IN ORDER TO REINFORCE THE BIOLOGICAL RELEVANCE OF EPIGENETIC DATA AND ITS TRANSLATIONAL USE IN PSYCHIATRY. OVERALL, WE SUGGEST THAT EPIGENETICS COULD PROVIDE NEW INSIGHTS INTO A MORE COMPREHENSIVE INTERPRETATION OF MENTAL ILLNESS AND MIGHT EVENTUALLY IMPROVE THE NOSOLOGY, TREATMENT, AND PREVENTION OF PSYCHIATRIC DISORDERS. 2018 5 6252 35 THE MICROBIOME AND CANCER: IMPLICATIONS FOR ONCOLOGY NURSING SCIENCE. BACKGROUND: APPROXIMATELY 1.6 MILLION AMERICANS WERE DIAGNOSED WITH CANCER IN 2014. TO COMBAT THEIR DISEASE, MANY INDIVIDUALS RECEIVED EITHER CURATIVE OR PALLIATIVE TREATMENTS THAT PRODUCED UNDESIRED SYMPTOMS. THESE SYMPTOMS, WHICH OFTEN CAUSE SIGNIFICANT DISTRESS FOR INDIVIDUALS COPING WITH CANCER, MAY SHARE BIOLOGIC UNDERPINNINGS SUCH AS EPIGENETIC CHANGES AND IMMUNE DYSREGULATION. ALTERATIONS IN THE NORMAL FLORA OF THE GUT MAY ALSO INFLUENCE CANCER SYMPTOMS. OBJECTIVE: THE AIM OF THIS REVIEW IS TO DESCRIBE THE EMERGING ROLE FOR THE GUT MICROBIOME IN CANCER RESEARCH, ESPECIALLY THE POTENTIAL RELATIONSHIP BETWEEN THE GUT MICROBIOME AND CANCER SYMPTOMS. METHODS: EXTANT LITERATURE WAS REVIEWED AND SYNTHESIZED. RESULTS: THE MAJORITY OF STUDIES LINKING THE GUT MICROBIOTA AND CANCER ARE ANIMAL MODELS AND FOCUS ON THE RELATIONSHIP BETWEEN DYSBIOSIS AND COLORECTAL CANCER. EMERGING EVIDENCE SUPPORTS THAT THE "GUT-BRAIN" CONNECTION IS A PLAUSIBLE MECHANISM FOR "PSYCHONEUROLOGICAL" CANCER SYMPTOMS SUCH AS DEPRESSION, PAIN, AND FATIGUE. CONCLUSIONS: THERE IS COMPELLING EVIDENCE THAT THE GUT MICROBIOTA AFFECTS CANCER VIA SEVERAL MECHANISMS, INCLUDING MICROBIAL DIVERSITY AND NUMBER, METABOLISM, AND/OR IMMUNE INITIATION. HOWEVER, MORE RESEARCH IS NECESSARY TO ELUCIDATE THESE MECHANISMS, PARTICULARLY AMONG A VARIETY OF CANCERS AND CANCER-RELATED SYMPTOMS. IMPLICATIONS FOR PRACTICE: A BETTER UNDERSTANDING OF THE ROLE OF THE GUT MICROBIOTA IN CANCER SYMPTOMS MAY LEAD TO THE DEVELOPMENT OF TARGETED INDIVIDUALIZED INTERVENTIONS AFFECTING THE GUT MICROBIOTA THAT PREVENT OR AMELIORATE DYSBIOSIS, THEREBY REDUCING SYMPTOMS. THESE INTERVENTIONS MAY EMPHASIZE SELF-CARE MANAGEMENT STRATEGIES ESSENTIAL FOR WELLNESS, SUCH AS DIET, NUTRITION, AND STRESS REDUCTION. 2016 6 4716 30 NON-GENETIC RATS MODELS FOR ATHEROSCLEROSIS RESEARCH: FROM PAST TO PRESENT. ATHEROSCLEROSIS IS AN INFLAMMATORY, PROGRESSIVE, AND CHRONIC ILLNESS THAT INVOLVES SEVERAL MOLECULAR AND EPIGENETIC FACTORS. DESPITE TREATMENT LIMITATIONS, CLINICAL AND THERAPEUTIC APPROACHES HAVE UNDENIABLY CHANGED RADICALLY IN RECENT DECADES THROUGH BETTER KNOWLEDGE OF THE PATHOPHYSIOLOGICAL BASIS OF THE DISEASE, WHICH HAS CONSIDERABLY IMPROVED PATIENTS' SURVIVAL AND QUALITY OF LIFE. SOME OF THESE ADVANCES ARE ATTRIBUTABLE TO BASIC BIOMEDICAL RESEARCH THAT PROVIDES INSIGHTS INTO A BETTER UNDERSTANDING AND IDENTIFICATION OF NEW MOLECULAR AND CELLULAR TARGETS FOR ATHEROSCLEROSIS TREATMENT. ALTHOUGH RODENT MODELS HAVE CONTRIBUTED SUBSTANTIALLY TO A BETTER UNDERSTANDING OF THE DEVELOPMENT OF ATHEROSCLEROSIS, THE ACCURACY OF THESE MODELS REMAINS CONTROVERSIAL. RESEARCH THAT UTILIZES GENETIC RODENT MODELS IS WELL ESTABLISHED, BUT THE USE OF SPECIFIC DIETS THAT ARE ASSOCIATED WITH OTHER RISK FACTORS (E.G., HYPERTENSION, HORMONE DEPRIVATION, AND PHARMACOLOGICAL TOOLS) IS STILL DEBATABLE. THE PRESENT REVIEW PROVIDES AN UPDATE ON NON-GENETIC RAT MODELS OF ATHEROSCLEROSIS AND AN OVERVIEW OF THE MAIN METHODOLOGIES THAT ARE CURRENTLY AVAILABLE. 2019 7 4591 24 NARRATIVE REVIEW OF THE COMPLEX INTERACTION BETWEEN PAIN AND TRAUMA IN CHILDREN: A FOCUS ON BIOLOGICAL MEMORY, PRECLINICAL DATA, AND EPIGENETIC PROCESSES. THE INCIDENCE AND COLLECTIVE IMPACT OF EARLY ADVERSE EXPERIENCES, TRAUMA, AND PAIN CONTINUE TO INCREASE. THIS UNDERSCORES THE URGENT NEED FOR TRANSLATIONAL EFFORTS BETWEEN CLINICAL AND PRECLINICAL RESEARCH TO BETTER UNDERSTAND THE UNDERLYING MECHANISMS AND DEVELOP EFFECTIVE THERAPEUTIC APPROACHES. AS OUR UNDERSTANDING OF THESE ISSUES IMPROVES FROM STUDIES IN CHILDREN AND ADOLESCENTS, WE CAN CREATE MORE PRECISE PRECLINICAL MODELS AND ULTIMATELY TRANSLATE OUR FINDINGS BACK TO CLINICAL PRACTICE. A MULTIDISCIPLINARY APPROACH IS ESSENTIAL FOR ADDRESSING THE COMPLEX AND WIDE-RANGING EFFECTS OF THESE EXPERIENCES ON INDIVIDUALS AND SOCIETY. THIS NARRATIVE REVIEW AIMS TO (1) DEFINE PAIN AND TRAUMA EXPERIENCES IN CHILDHOOD AND ADOLESCENTS, (2) DISCUSS THE RELATIONSHIP BETWEEN PAIN AND TRAUMA, (3) CONSIDER THE ROLE OF BIOLOGICAL MEMORY, (4) DECIPHER THE RELATIONSHIP BETWEEN PAIN AND TRAUMA USING PRECLINICAL DATA, AND (5) EXAMINE THE ROLE OF THE ENVIRONMENT BY INTRODUCING THE IMPORTANCE OF EPIGENETIC PROCESSES. THE ULTIMATE SCOPE IS TO BETTER UNDERSTAND THE WIDE-RANGING EFFECTS OF TRAUMA, ABUSE, AND CHRONIC PAIN ON CHILDREN AND ADOLESCENTS, HOW THEY OCCUR, AND HOW TO PREVENT OR MITIGATE THEIR EFFECTS AND DEVELOP EFFECTIVE TREATMENT STRATEGIES THAT ADDRESS BOTH THE UNDERLYING CAUSES AND THE ASSOCIATED PHYSIOLOGICAL AND PSYCHOLOGICAL EFFECTS. 2023 8 724 28 CAN GENETICS GUIDE EXERCISE PRESCRIPTIONS IN OSTEOARTHRITIS? OSTEOARTHRITIS (OA) IS THE MOST COMMON FORM OF ARTHRITIS AND HAS A MULTIFACTORIAL ETIOLOGY. CURRENT MANAGEMENT FOR OA FOCUSES ON MINIMIZING PAIN AND FUNCTIONAL LOSS, TYPICALLY INVOLVING PHARMACOLOGICAL, PHYSICAL, PSYCHOSOCIAL, AND MIND-BODY INTERVENTIONS. HOWEVER, THERE REMAIN CHALLENGES IN DETERMINING WHICH PATIENTS WILL BENEFIT MOST FROM WHICH INTERVENTIONS. ALTHOUGH EXERCISE-BASED INTERVENTIONS ARE RECOMMENDED AS FIRST-LINE TREATMENTS AND ARE KNOWN TO BE BENEFICIAL FOR MANAGING BOTH THE DISEASE AND ILLNESS OF OA, THE OPTIMAL EXERCISE "PRESCRIPTION" IS UNKNOWN, DUE IN PART TO OUR LIMITED UNDERSTANDING OF THE PRECISE MECHANISMS UNDERLYING ITS ACTION. HERE WE PRESENT OUR PERSPECTIVE ON THE POTENTIAL ROLE OF GENETICS IN GUIDING EXERCISE PRESCRIPTION FOR PERSONS WITH OA. WE DESCRIBE KEY PUBLICATIONS IN THE AREAS OF EXERCISE AND OA, GENETICS AND OA, AND EXERCISE AND GENETICS, AND POINT TO A PAUCITY OF KNOWLEDGE AT THE INTERSECTION OF EXERCISE, GENETICS, AND OA. WE SUGGEST THERE IS EMERGING EVIDENCE TO SUPPORT THE USE OF GENETICS AND EPIGENETICS TO EXPLAIN THE BENEFICIAL EFFECTS OF EXERCISE FOR OA. WE IDENTIFY MISSING LINKS IN THE EXISTING RESEARCH RELATING TO EXERCISE, GENETICS, AND OA, AND HIGHLIGHT EPIGENETICS AS A PROMISING MECHANISM THROUGH WHICH ENVIRONMENTAL EXPOSURES SUCH AS EXERCISE MAY IMPACT OA OUTCOMES. WE ANTICIPATE FUTURE STUDIES WILL IMPROVE OUR UNDERSTANDING OF HOW GENETIC AND EPIGENETIC FACTORS MEDIATE EXERCISE-BASED INTERVENTIONS TO SUPPORT IMPLEMENTATION AND ULTIMATELY IMPROVE OA PATIENT CARE. 2022 9 4743 22 NOVEL INSIGHTS FROM GENETIC AND EPIGENETIC STUDIES IN UNDERSTANDING THE COMPLEX URAEMIC PHENOTYPE. LIKE IN MANY OTHER COMMON COMPLEX DISORDERS, STUDIES OF CHRONIC KIDNEY DISEASE (CKD) CAN NOW MAKE USE OF THE INCREASING KNOWLEDGE OF THE HUMAN GENOME, ITS VARIATIONS AND IMPACT ON DISEASE SUSCEPTIBILITY, INITIATION, PROGRESSION AND COMPLICATIONS. SUCH STUDIES ARE FACILITATED BY NOVEL READILY AVAILABLE HIGH THROUGH-PUT GENOTYPING METHODS AND SOPHISTICATED ANALYTICAL APPROACHES TO SCAN THE GENOME FOR DNA VARIATIONS AND EPIGENETIC MODIFICATIONS. HERE, WE REVIEW SOME OF THE RECENT DISCOVERIES THAT HAVE EMERGED FROM THESE STUDIES AND EXPANDED OUR KNOWLEDGE OF GENETIC RISK LOCI AND EPIGENETIC MARKERS IN CKD PATHOPHYSIOLOGY. OBSTACLES AND PRACTICAL ISSUES IN THIS FIELD ARE DISCUSSED. 2014 10 6863 26 [ONE AUTISM, SEVERAL AUTISMS. PHENOTYPICAL VARIABILITY IN AUTISM SPECTRUM DISORDERS]. INTRODUCTION: AUTISM SPECTRUM DISORDERS (ASD) ARE A HETEROGENEOUS GROUP OF DISORDERS THAT BEGIN IN THE EARLY MONTHS OF LIFE AND FOLLOW A CHRONIC PROGRESSION. THEY HAVE A BIOLOGICAL ORIGIN, WITH COMPLEX AETIOLOGICAL FACTORS THAT INVOLVE DIFFERENT GENETIC, EPIGENETIC AND ENVIRONMENTAL MECHANISMS THAT INTERACT WITH ONE ANOTHER. AIM: TO REVIEW THE MAIN FACTORS THAT VARY THE PRESENTATION OF AUTISM TAKING INTO ACCOUNT THE MOST RECENT SCIENTIFIC EVIDENCE. DEVELOPMENT: ASPECTS RELATED WITH THE DEVELOPMENT OF SYMPTOMS, GENDER, COMORBIDITY, AGE AND AETIOLOGY DETERMINE THE VARIABILITY IN THE CLINICAL PRESENTATION OF ASD. CONCLUSIONS: AUTISM IS HIGHLY HETEROGENEOUS AND IS PHENOTYPICALLY RELATED, AT LEAST IN PART, WITH A WIDE RANGE OF CAUSATIONS, WHICH RESEARCHERS HAVE BEGUN TO UNRAVEL BUT WHICH ARE STILL LARGELY UNKNOWN. AETIOLOGICAL RESEARCH, ESPECIALLY IN THE AREA OF GENETICS, WILL MAKE IT POSSIBLE TO IDENTIFY DIFFERENT HOMOGENEOUS SUBGROUPS WITH THEIR CORRESPONDING PHENOTYPES, WHILE ALSO OPENING UP THE WAY TO POSSIBLE THERAPEUTIC ALTERNATIVES IN THE FUTURE. 2016 11 3404 26 HOW EPIGENETICS IMPACTS ON HUMAN DISEASES. EPIGENETICS IS A RAPIDLY GROWING FIELD OF BIOLOGY THAT STUDIES THE CHANGES IN GENE EXPRESSION THAT ARE NOT DUE TO ALTERATIONS IN THE DNA SEQUENCE BUT RATHER THE CHEMICAL MODIFICATIONS OF DNA AND ITS ASSOCIATED PROTEINS. EPIGENETIC MECHANISMS CAN PROFOUNDLY INFLUENCE GENE EXPRESSION, CELL DIFFERENTIATION, TISSUE DEVELOPMENT, AND DISEASE SUSCEPTIBILITY. UNDERSTANDING EPIGENETIC CHANGES IS ESSENTIAL TO ELUCIDATE THE MECHANISMS UNDERLYING THE INCREASINGLY RECOGNIZED ROLE OF ENVIRONMENTAL AND LIFESTYLE FACTORS IN HEALTH AND DISEASE AND THE INTERGENERATIONAL TRANSMISSION OF PHENOTYPES. RECENT STUDIES SUGGEST EPIGENETICS MAY BE CRITICAL IN VARIOUS DISEASES, FROM CARDIOVASCULAR DISEASE AND CANCER TO NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS. EPIGENETIC MODIFICATIONS ARE POTENTIALLY REVERSIBLE AND COULD PROVIDE NEW THERAPEUTIC AVENUES FOR TREATING THESE DISEASES USING EPIGENETIC MODULATORS. MOREOVER, EPIGENETICS PROVIDE INSIGHT INTO DISEASE PATHOGENESIS AND BIOMARKERS FOR DISEASE DIAGNOSIS AND RISK STRATIFICATION. NEVERTHELESS, EPIGENETIC INTERVENTIONS HAVE THE POTENTIAL FOR UNINTENDED CONSEQUENCES AND MAY POTENTIALLY LEAD TO INCREASED RISKS OF UNEXPECTED OUTCOMES, SUCH AS ADVERSE DRUG REACTIONS, DEVELOPMENTAL ABNORMALITIES, AND CANCER. THEREFORE, RIGOROUS STUDIES ARE ESSENTIAL TO MINIMIZE THE RISKS ASSOCIATED WITH EPIGENETIC THERAPIES AND TO DEVELOP SAFE AND EFFECTIVE INTERVENTIONS FOR IMPROVING HUMAN HEALTH. THIS ARTICLE PROVIDES A SYNTHETIC AND HISTORICAL VIEW OF THE ORIGIN OF EPIGENETICS AND SOME OF THE MOST RELEVANT ACHIEVEMENTS. 2023 12 1248 33 CURRENT EVIDENCE FOR BIOLOGICAL BIOMARKERS AND MECHANISMS UNDERLYING ACUTE TO CHRONIC PAIN TRANSITION ACROSS THE PEDIATRIC AGE SPECTRUM. CHRONIC PAIN IS HIGHLY PREVALENT IN THE PEDIATRIC POPULATION. MANY FACTORS ARE INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN. CURRENTLY, THERE ARE CONCEPTUAL MODELS PROPOSED, BUT THEY LACK A MECHANISTICALLY SOUND INTEGRATED THEORY CONSIDERING THE STAGES OF CHILD DEVELOPMENT. OBJECTIVE BIOMARKERS ARE CRITICALLY NEEDED FOR THE DIAGNOSIS, RISK STRATIFICATION, AND PROGNOSIS OF THE PATHOLOGICAL STAGES OF PAIN CHRONIFICATION. IN THIS ARTICLE, WE SUMMARIZE THE CURRENT EVIDENCE ON MECHANISMS AND BIOMARKERS OF ACUTE TO CHRONIC PAIN TRANSITIONS IN INFANTS AND CHILDREN THROUGH THE DEVELOPMENTAL LENS. THE GOAL IS TO IDENTIFY GAPS AND OUTLINE FUTURE DIRECTIONS FOR BASIC AND CLINICAL RESEARCH TOWARD A DEVELOPMENTALLY INFORMED THEORY OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. AT THE OUTSET, THE IMPORTANCE OF OBJECTIVE BIOMARKERS FOR CHRONIFICATION OF PAIN IN CHILDREN IS OUTLINED, FOLLOWED BY A SUMMARY OF THE CURRENT EVIDENCE ON THE MECHANISMS OF ACUTE TO CHRONIC PAIN TRANSITION IN ADULTS, IN ORDER TO CONTRAST WITH THE DEVELOPMENTAL MECHANISMS OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. EVIDENCE IS PRESENTED TO SHOW THAT CHRONIC PAIN MAY HAVE ITS ORIGIN FROM INSULTS EARLY IN LIFE, WHICH PRIME THE CHILD FOR THE DEVELOPMENT OF CHRONIC PAIN IN LATER LIFE. FURTHERMORE, AVAILABLE GENETIC, EPIGENETIC, PSYCHOPHYSICAL, ELECTROPHYSIOLOGICAL, NEUROIMAGING, NEUROIMMUNE, AND SEX MECHANISMS ARE DESCRIBED IN INFANTS AND OLDER CHILDREN. IN CONCLUSION, FUTURE DIRECTIONS ARE DISCUSSED WITH A FOCUS ON RESEARCH GAPS, TRANSLATIONAL AND CLINICAL IMPLICATIONS. UTILIZATION OF DEVELOPMENTAL MECHANISMS FRAMEWORK TO INFORM CLINICAL DECISION-MAKING AND STRATEGIES FOR PREVENTION AND MANAGEMENT OF ACUTE TO CHRONIC PAIN TRANSITIONS IN CHILDREN, IS HIGHLIGHTED. 2023 13 4277 26 MICROGLIA SEQUELAE: BRAIN SIGNATURE OF INNATE IMMUNITY IN SCHIZOPHRENIA. SCHIZOPHRENIA IS A PSYCHIATRIC DISORDER WITH SIGNIFICANT IMPACT ON INDIVIDUALS AND SOCIETY. THE CURRENT PHARMACOLOGIC TREATMENT, WHICH PRINCIPALLY ALLEVIATES PSYCHOSIS, IS FOCUSED ON NEUROTRANSMITTERS MODULATION, RELYING ON DRUGS WITH SEVERE SIDE EFFECTS AND INEFFECTIVENESS IN A SIGNIFICANT PERCENTAGE OF CASES. THEREFORE, AND DUE TO DIFFICULTIES INHERENT TO DIAGNOSIS AND TREATMENT, IT IS VITAL TO REASSESS ALTERNATIVE CELLULAR AND MOLECULAR DRUG TARGETS. DISTINCT RISK FACTORS - GENETIC, DEVELOPMENTAL, EPIGENETIC, AND ENVIRONMENTAL - HAVE BEEN ASSOCIATED WITH DISEASE ONSET AND PROGRESSION, GIVING RISE TO THE PROPOSAL OF DIFFERENT PATHOPHYSIOLOGICAL MECHANISMS AND PUTATIVE PHARMACOLOGICAL TARGETS. IMMUNITY IS INVOLVED AND, PARTICULARLY MICROGLIA - INNATE IMMUNE CELLS OF THE CENTRAL NERVOUS SYSTEM, CRITICALLY INVOLVED IN BRAIN DEVELOPMENT - HAVE CAPTURED ATTENTION AS CELLULAR PLAYERS. MICROGLIA UNDERGO MARKED MORPHOLOGIC AND FUNCTIONAL ALTERATIONS IN THE HUMAN DISEASE, AS WELL AS IN ANIMAL MODELS OF SCHIZOPHRENIA, AS REPORTED IN SEVERAL ORIGINAL PAPERS. WE CLUSTER THE MAIN FINDINGS OF CLINICAL STUDIES BY GROUPS OF PATIENTS: (1) AT ULTRA-HIGH RISK OF PSYCHOSIS, (2) WITH A FIRST EPISODE OF PSYCHOSIS OR RECENT-ONSET SCHIZOPHRENIA, AND (3) WITH CHRONIC SCHIZOPHRENIA; IN TRANSLATIONAL STUDIES, WE HIGHLIGHT THE TIME WINDOW OF APPEARANCE OF PARTICULAR MICROGLIA ALTERATIONS IN THE MOST WELL STUDIED ANIMAL MODEL IN THE FIELD (MATERNAL IMMUNE ACTIVATION). THE ORGANIZATION OF CLINICAL AND TRANSLATIONAL FINDINGS BASED ON SCHIZOPHRENIA-ASSOCIATED MICROGLIA CHANGES IN DIFFERENT PHASES OF THE DISEASE COURSE MAY HELP DEFINING A TEMPORAL PATTERN OF MICROGLIA CHANGES AND MAY DRIVE THE DESIGN OF NOVEL THERAPEUTIC STRATEGIES. 2022 14 4273 27 MICROBIOTA AND EPIGENETICS: HEALTH IMPACT. EPIGENETIC CHANGES ASSOCIATED WITH DISEASE DEVELOPMENT AND PROGRESSIONS ARE OF INCREASING IMPORTANCE BECAUSE OF THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. SEVERAL EPIGENETIC CHANGES ASSOCIATED WITH CHRONIC METABOLIC DISORDERS HAVE BEEN STUDIED IN VARIOUS DISEASES. EPIGENETIC CHANGES ARE MOSTLY MODULATED BY ENVIRONMENTAL FACTORS, INCLUDING THE HUMAN MICROBIOTA LIVING IN DIFFERENT PARTS OF OUR BODIES. THE MICROBIAL STRUCTURAL COMPONENTS AND THE MICROBIALLY DERIVED METABOLITES DIRECTLY INTERACT WITH HOST CELLS, THEREBY MAINTAINING HOMEOSTASIS. MICROBIOME DYSBIOSIS, ON THE OTHER HAND, IS KNOWN TO PRODUCE ELEVATED LEVELS OF DISEASE-LINKED METABOLITES, WHICH MAY DIRECTLY AFFECT A HOST METABOLIC PATHWAY OR INDUCE EPIGENETIC CHANGES THAT CAN LEAD TO DISEASE DEVELOPMENT. DESPITE THEIR IMPORTANT ROLE IN HOST PHYSIOLOGY AND SIGNAL TRANSDUCTION, THERE HAS BEEN LITTLE RESEARCH INTO THE MECHANICS AND PATHWAYS ASSOCIATED WITH EPIGENETIC MODIFICATIONS. THIS CHAPTER FOCUSES ON THE RELATIONSHIP BETWEEN MICROBES AND THEIR EPIGENETIC EFFECTS IN DISEASED PATHOLOGY, AS WELL AS ON THE REGULATION AND METABOLISM OF THE DIETARY OPTIONS AVAILABLE TO THE MICROBES. FURTHERMORE, THIS CHAPTER ALSO PROVIDES A PROSPECTIVE LINK BETWEEN THESE TWO IMPORTANT PHENOMENA, TERMED "MICROBIOME AND EPIGENETICS." 2023 15 3016 26 GENETICS AND EPIGENETICS OF IBD. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INTERMITTENT INFLAMMATORY DISORDERS OF THE GASTROINTESTINAL TRACT OF UNKNOWN ETIOLOGY BUT A CLEAR GENETIC PREDISPOSITION. PROMPTED BY THE FIRST INVESTIGATIONS ON IBD FAMILIES AND TWINS, THE GENETIC AND EPIGENETIC STUDIES HAVE PRODUCED AN UNPRECEDENTED AMOUNT OF INFORMATION IN COMPARISON WITH OTHER IMMUNE-MEDIATED OR COMPLEX DISEASES. NEW INFLAMMATORY PATHWAYS AND POSSIBLE MECHANISMS OF ACTION HAVE BEEN DISCLOSED, POTENTIALLY LEADING TO NEW-TARGETED THERAPY. HOWEVER, THE IDENTIFICATION OF GENETIC MARKERS DUE TO THE GREAT DISEASE HETEROGENEITY AND THE OVERWHELMING CONTRIBUTION OF ENVIRONMENTAL RISK FACTORS HAS NOT MODIFIED YET THE DISEASE MANAGEMENT. THE POSSIBILITY FOR THE FUTURE OF A BETTER PREDICTION OF DISEASE COURSE, RESPONSE TO THERAPY AND THERAPY-RELATED ADVERSE EVENTS MAY ALLOW A MORE EFFICIENT AND PERSONALIZED STRATEGY. THIS REVIEW WILL FOCUS ON MORE RECENT DISCOVERIES THAT MAY POTENTIALLY BE OF RELEVANCE IN DAILY CLINICAL PRACTICE. 2020 16 4342 28 MINIREVIEW: EPIGENETICS OF OBESITY AND DIABETES IN HUMANS. UNDERSTANDING THE DETERMINANTS OF HUMAN HEALTH AND DISEASE IS OVERWHELMINGLY COMPLEX, PARTICULARLY FOR COMMON, LATE-ONSET, CHRONIC DISORDERS, SUCH AS OBESITY AND DIABETES. ELUCIDATING THE GENETIC AND ENVIRONMENTAL FACTORS THAT INFLUENCE SUSCEPTIBILITY TO DISRUPTIONS IN ENERGY HOMEOSTASIS AND METABOLIC REGULATION REMAIN A CHALLENGE, AND PROGRESS WILL ENTAIL THE INTEGRATION OF MULTIPLE ASSESSMENTS OF TEMPORALLY DYNAMIC ENVIRONMENTAL EXPOSURES IN THE CONTEXT OF EACH INDIVIDUAL'S GENOTYPE. TO MEET THIS CHALLENGE, RESEARCHERS ARE INCREASINGLY EXPLORING THE EPIGENOME, WHICH IS THE MALLEABLE INTERFACE OF GENE-ENVIRONMENT INTERACTIONS. EPIGENETIC VARIATION, WHETHER INNATE OR INDUCED, CONTRIBUTES TO VARIATION IN GENE EXPRESSION, THE RANGE OF POTENTIAL INDIVIDUAL RESPONSES TO INTERNAL AND EXTERNAL CUES, AND RISK FOR METABOLIC DISEASE. ULTIMATELY, ADVANCEMENT IN OUR UNDERSTANDING OF CHRONIC DISEASE SUSCEPTIBILITY IN HUMANS WILL DEPEND ON REFINEMENT OF EXPOSURE ASSESSMENT TOOLS AND SYSTEMS BIOLOGY APPROACHES TO INTERPRETATION. IN THIS REVIEW, WE PRESENT RECENT PROGRESS IN EPIGENETICS OF HUMAN OBESITY AND DIABETES, EXISTING CHALLENGES, AND THE POTENTIAL FOR NEW APPROACHES TO UNRAVEL THE COMPLEX BIOLOGY OF METABOLIC DYSREGULATION. 2012 17 2404 32 EPIGENETIC RESEARCH IN MULTIPLE SCLEROSIS: PROGRESS, CHALLENGES, AND OPPORTUNITIES. MULTIPLE SCLEROSIS (MS) IS A CHRONIC INFLAMMATORY AND DEMYELINATING DISEASE OF THE CENTRAL NERVOUS SYSTEM. MS LIKELY RESULTS FROM A COMPLEX INTERPLAY BETWEEN PREDISPOSING CAUSAL GENE VARIANTS (THE STRONGEST INFLUENCE COMING FROM HLA CLASS II LOCUS) AND ENVIRONMENTAL RISK FACTORS SUCH AS SMOKING, INFECTIOUS MONONUCLEOSIS, AND LACK OF SUN EXPOSURE/VITAMIN D. HOWEVER, LITTLE IS KNOWN ABOUT THE MECHANISMS UNDERLYING MS DEVELOPMENT AND PROGRESSION. MOREOVER, THE CLINICAL HETEROGENEITY AND VARIABLE RESPONSE TO TREATMENT REPRESENT ADDITIONAL CHALLENGES TO A COMPREHENSIVE UNDERSTANDING AND EFFICIENT TREATMENT OF DISEASE. EPIGENETIC PROCESSES, SUCH AS DNA METHYLATION AND HISTONE POSTTRANSLATIONAL MODIFICATIONS, INTEGRATE INFLUENCES FROM THE GENES AND THE ENVIRONMENT TO REGULATE GENE EXPRESSION ACCORDINGLY. STUDYING EPIGENETIC MODIFICATIONS, WHICH ARE STABLE AND REVERSIBLE, MAY PROVIDE AN ALTERNATIVE APPROACH TO BETTER UNDERSTAND AND MANAGE DISEASE. WE HERE AIM TO REVIEW FINDINGS FROM EPIGENETIC STUDIES IN MS AND FURTHER DISCUSS THE CHALLENGES AND CLINICAL OPPORTUNITIES ARISING FROM EPIGENETIC RESEARCH, MANY OF WHICH APPLY TO OTHER DISEASES WITH SIMILAR COMPLEX ETIOLOGY. A GROWING BODY OF EVIDENCE SUPPORTS A ROLE OF EPIGENETIC PROCESSES IN THE MECHANISMS UNDERLYING IMMUNE PATHOGENESIS AND NERVOUS SYSTEM DYSFUNCTION IN MS. HOWEVER, DISPARITIES BETWEEN STUDIES SHED LIGHT ON THE NEED TO CONSIDER POSSIBLE CONFOUNDERS AND METHODOLOGICAL LIMITATIONS FOR A BETTER INTERPRETATION OF THE DATA. NEVERTHELESS, TRANSLATIONAL USE OF EPIGENETICS MIGHT OFFER NEW OPPORTUNITIES IN EPIGENETIC-BASED DIAGNOSTICS AND THERAPEUTIC TOOLS FOR A PERSONALIZED CARE OF MS PATIENTS. 2017 18 6211 29 THE INTERPLAY BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN IN HEALTH AND DISEASE: POTENTIAL ROLE OF AUTONOMIC REGULATION AND EPIGENETIC MECHANISMS. OXIDATIVE STRESS CAN BE INDUCED BY VARIOUS STIMULI AND ALTERED IN CERTAIN CONDITIONS, INCLUDING EXERCISE AND PAIN. ALTHOUGH MANY STUDIES HAVE INVESTIGATED OXIDATIVE STRESS IN RELATION TO EITHER EXERCISE OR PAIN, THE LITERATURE PRESENTS CONFLICTING RESULTS. THEREFORE, THIS REVIEW CRITICALLY DISCUSSES EXISTING LITERATURE ABOUT THIS TOPIC, AIMING TO PROVIDE A CLEAR OVERVIEW OF KNOWN INTERACTIONS BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN IN HEALTHY PEOPLE AS WELL AS IN PEOPLE WITH CHRONIC PAIN, AND TO HIGHLIGHT POSSIBLE CONFOUNDING FACTORS TO KEEP IN MIND WHEN REFLECTING ON THESE INTERACTIONS. IN ADDITION, AUTONOMIC REGULATION AND EPIGENETIC MECHANISMS ARE PROPOSED AS POTENTIAL MECHANISMS OF ACTION UNDERLYING THE INTERPLAY BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN. THIS REVIEW HIGHLIGHTS THAT THE RELATION BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN IS POORLY UNDERSTOOD AND NOT STRAIGHTFORWARD, AS IT IS DEPENDENT ON THE CHARACTERISTICS OF EXERCISE, BUT ALSO ON WHICH POPULATION IS INVESTIGATED. TO BE ABLE TO COMPARE STUDIES ON THIS TOPIC, STRICT GUIDELINES SHOULD BE DEVELOPED TO LIMIT THE EFFECT OF SEVERAL CONFOUNDING FACTORS. THIS WAY, THE TRUE INTERPLAY BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN, AND THE UNDERLYING MECHANISMS OF ACTION CAN BE REVEALED AND VALIDATED VIA INDEPENDENT STUDIES. 2020 19 4325 26 MICRORNAS IN THE EVALUATION AND POTENTIAL TREATMENT OF LIVER DISEASES. ACUTE AND CHRONIC LIVER DISEASE CONTINUE TO RESULT IN SIGNIFICANT MORBIDITY AND MORTALITY OF PATIENTS, ALONG WITH INCREASING BURDEN ON THEIR FAMILIES, SOCIETY AND THE HEALTH CARE SYSTEM. THIS IN PART IS DUE TO INCREASED INCIDENCE OF LIVER DISEASE ASSOCIATED FACTORS SUCH AS METABOLIC SYNDROME; IMPROVED SURVIVAL OF PATIENTS WITH CHRONIC PREDISPOSING CONDITIONS SUCH AS HIV; AS WELL AS ADVANCES IN THE FIELD OF TRANSPLANTATION AND ASSOCIATED CARE LEADING TO IMPROVED SURVIVAL. THE FACT THAT ONE DISEASE CAN RESULT IN DIFFERENT MANIFESTATIONS AND OUTCOMES HIGHLIGHTS THE NEED FOR IMPROVED UNDERSTANDING OF NOT JUST GENETIC PHENOMENON PREDISPOSING TO A CONDITION, BUT ADDITIONALLY THE ROLE OF EPIGENETIC AND ENVIRONMENTAL FACTORS LEADING TO THE PHENOTYPE OF THE DISEASE. IT IS NOT SURPRISING THAT PROVIDERS CONTINUE TO FACE DAILY CHALLENGES PERTAINING TO DIAGNOSTIC ACCURACY, PROGNOSTICATION OF DISEASE SEVERITY, PROGRESSION, AND RESPONSE TO THERAPIES. A NUMBER OF THESE CHALLENGES CAN BE ADDRESSED BY INCORPORATING A PERSONALIZED APPROACH OF MANAGEMENT TO THE CURRENT PARADIGM OF CARE. RECENT ADVANCES IN THE FIELDS OF MOLECULAR BIOLOGY AND GENETICS HAVE PAVED THE WAY TO MORE ACCURATE, INDIVIDUALIZED AND PRECISE APPROACH TO CARING FOR LIVER DISEASE. THE STUDY OF MICRORNAS AND THEIR ROLE IN BOTH HEALTHY AND DISEASED LIVERS IS ONE EXAMPLE OF SUCH ADVANCES. AS THESE SMALL, NON-CODING RNAS WORK ON FINE-TUNING OF CELLULAR ACTIVITIES AND ORGAN FUNCTION IN A DYNAMIC AND PRECISE FASHION, THEY PROVIDE US A GOLDEN OPPORTUNITY TO ADVANCE THE FIELD OF HEPATOLOGY. THE STUDY OF MICRORNAS IN LIVER DISEASE PROMISES TREMENDOUS IMPROVEMENT IN HEPATOLOGY AND IS LIKELY TO LAY THE FOUNDATION TOWARDS A PERSONALIZED APPROACH IN LIVER DISEASE. 2016 20 38 21 A COMMON ROLE FOR PSYCHOTROPIC MEDICATIONS: MEMORY IMPAIRMENT. THE PSYCHOPATHOLOGIC PROFILE OF MENTAL DISORDERS IS VERY DIVERSE AND PSYCHOTROPIC MEDICATIONS USED TO TREAT THEM DIFFER IN THEIR CHEMICAL STRUCTURE. NEVERTHELESS, THESE DRUGS SHARE THESE FOUR CHARACTERISTICS: DELAYED ONSET OF CLINICAL RESPONSE, NOT ONE OF THEM CAN BE SAID TO CURE, THERE IS A HIGH NUMBER OF NON-RESPONDERS, AND THE MECHANISM RESPONSIBLE FOR THEIR THERAPEUTIC ACTION IS NOT KNOWN. IT IS HYPOTHESIZED THAT THE ACTION OF PSYCHOTROPIC MEDICATIONS IS MEMORY IMPAIRMENT, UNDERSTANDING MEMORY AS THE TRACE LEFT IN THE NERVOUS SYSTEM NOT ONLY BY INDIVIDUAL EXPERIENCES BUT ALSO BY GENETIC AND EPIGENETIC PHENOMENA. IT IS SUGGESTED THAT IT WOULD BE BENEFICIAL TO TRANSLATE SOME RESEARCH STRATEGIES FROM THE NEUROBIOLOGY OF LEARNING AND MEMORY TO THE STUDY OF THE EFFECTS OF PSYCHOTROPIC MEDICATIONS. THE HYPOTHESIS IS BRIEFLY ASSESSED ACCORDING TO THE FOLLOWING THREE CRITERIA: (A). THE COMPARISON BETWEEN THE MOLECULAR EFFECTS OF PSYCHOTROPIC MEDICATIONS AND THE SO-CALLED MOLECULAR BIOLOGY OF LEARNING AND MEMORY, (B). THE EFFECTS OF THESE DRUGS, PREFERENTIALLY AFTER CHRONIC USE, ON MEMORY TESTS, AND (C). THE EFFECTS OF DRUGS THAT IMPAIR MEMORY ON TESTS USED FOR SCREENING PSYCHOTROPIC MEDICATIONS. FINALLY, SOME GENERAL SUGGESTIONS FOR FUTURE RESEARCH ARE POINTED OUT. 2003