1 5037 159 PHARMACOGENETICS IN PAIN TREATMENT. PAIN IS AN UNPLEASANT FEELING USUALLY RESULTING FROM TISSUE DAMAGE THAT CAN PERSIST ALONG WEEKS, MONTHS, OR EVEN YEARS AFTER THE INJURY, TURNING INTO PATHOLOGICAL CHRONIC PAIN, THE LEADING CAUSE OF DISABILITY. CURRENTLY, PHARMACOLOGY INTERVENTIONS ARE USUALLY THE FIRST-LINE THERAPY BUT THERE IS A HIGHLY VARIABLE ANALGESIC DRUG RESPONSE. PHARMACOGENETICS (PGX) OFFERS A MEANS TO IDENTIFY GENETIC BIOMARKERS THAT CAN PREDICT INDIVIDUAL ANALGESIC RESPONSE OPENING DOORS TO PRECISION MEDICINE. PGX ANALYZE THE WAY IN WHICH THE PRESENCE OF VARIATIONS IN THE DNA SEQUENCE (SINGLE-NUCLEOTIDE POLYMORPHISMS, SNPS) COULD BE RESPONSIBLE FOR PORTIONS OF THE POPULATION REACHING DIFFERENT LEVELS OF PAIN RELIEF (PHENOTYPE) DUE TO GENE INTERFERENCE IN THE DRUG MECHANISM OF ACTION (PHARMACODYNAMICS) AND/OR ITS CONCENTRATION AT THE PLACE OF ACTION (PHARMACOKINETICS). SNPS IN THE CYTOCHROME P450 ENZYMES GENES (CYP2D6) INFLUENCE METABOLISM OF CODEINE, TRAMADOL, HYDROCODONE, OXYCODONE, AND TRICYCLIC ANTIDEPRESSANTS. BLOOD CONCENTRATIONS OF SOME NSAIDS DEPEND ON CYP2C9 AND/OR CYP2C8 ACTIVITY. ADDITIONAL CANDIDATE GENES ENCODE FOR OPIOID RECEPTORS, TRANSPORTERS, AND OTHER MOLECULES IMPORTANT FOR PHARMACOTHERAPY IN PAIN MANAGEMENT. HOWEVER, PGX STUDIES ARE OFTEN CONTRADICTORY, SLOWING THE UPTAKE OF THIS INFORMATION. THIS IS LIKELY DUE, IN LARGE PART, TO A LACK OF ROBUST EVIDENCE DEMONSTRATING CLINICAL UTILITY AND TO ITS POLYGENIC RESPONSE MODULATED BY OTHER EXOGENOUS OR EPIGENETICS FACTORS. NOVEL THERAPIES, INCLUDING TARGETING OF EPIGENETIC CHANGES AND GENE THERAPY-BASED APPROACHES, BROADEN FUTURE OPTIONS TO IMPROVE UNDERSTANDING OF PAIN AND THE TREATMENT OF PEOPLE WHO SUFFER IT. 2018 2 5042 53 PHARMACOGENOMICS IN PAIN TREATMENT. THE EXPERIENCE OF CHRONIC PAIN IS ONE OF THE COMMONEST REASONS FOR SEEKING MEDICAL ATTENTION, BEING A MAJOR ISSUE IN CLINICAL PRACTICE. WHILE PAIN IS A UNIVERSAL EXPERIENCE, ONLY A SMALL PROPORTION OF PEOPLE WHO FELT PAIN DEVELOP PAIN SYNDROMES. IN ADDITION, PAINKILLERS ARE ASSOCIATED WITH WIDE INTER-INDIVIDUAL VARIABILITY IN THE ANALGESIC RESPONSE. THIS MAY BE PARTLY EXPLAINED BY THE PRESENCE OF SINGLE NUCLEOTIDE POLYMORPHISMS IN GENES ENCODING MOLECULAR ENTITIES INVOLVED IN PHARMACODYNAMICS AND PHARMACOKINETICS. HOWEVER, UPTAKE OF THIS INFORMATION HAS BEEN SLOW DUE IN LARGE PART TO THE LACK OF ROBUST EVIDENCES DEMONSTRATING CLINICAL UTILITY. FURTHERMORE, NOVEL THERAPIES, INCLUDING TARGETING OF EPIGENETIC CHANGES AND GENE THERAPY-BASED APPROACHES ARE FURTHER BROADENING FUTURE OPTIONS FOR THE TREATMENT OF CHRONIC PAIN. THE AIM OF THIS ARTICLE IS TO REVIEW THE EVIDENCES BEHIND PHARMACOGENETICS (PGX) TO INDIVIDUALIZE THERAPY (BOOSTING THE EFFICACY AND MINIMIZING POTENTIAL TOXICITY) AND GENES IMPLICATED IN PAIN MEDICINE, IN TWO PARTS: (I) GENETIC VARIABILITY WITH PAIN SENSITIVITY AND ANALGESIC RESPONSE; AND (II) PHARMACOLOGICAL CONCEPTS APPLIED ON PGX. 2016 3 6480 38 TOWARDS PRECISION MEDICINE IN GENERALIZED ANXIETY DISORDER: REVIEW OF GENETICS AND PHARMACO(EPI)GENETICS. GENERALIZED ANXIETY DISORDER (GAD) IS A PREVALENT AND CHRONIC MENTAL DISORDER THAT ELICITS WIDESPREAD FUNCTIONAL IMPAIRMENT. GIVEN THE HIGH DEGREE OF NON-RESPONSE/PARTIAL RESPONSE AMONG PATIENTS WITH GAD TO AVAILABLE PHARMACOLOGICAL TREATMENTS, THERE IS A STRONG NEED FOR NOVEL APPROACHES THAT CAN OPTIMIZE OUTCOMES, AND LEAD TO MEDICATIONS THAT ARE SAFER AND MORE EFFECTIVE. ALTHOUGH INVESTIGATIONS HAVE IDENTIFIED INTERESTING TARGETS PREDICTING TREATMENT RESPONSE THROUGH PHARMACOGENETICS (PGX), PHARMACO-EPIGENETICS, AND NEUROIMAGING METHODS, THESE STUDIES ARE OFTEN SOLITARY, NOT REPLICATED, AND CARRY SEVERAL LIMITATIONS. THIS REVIEW PROVIDES AN OVERVIEW OF THE CURRENT STATUS OF GAD GENETICS AND PGX AND PRESENTS POTENTIAL STRATEGIES TO IMPROVE TREATMENT RESPONSE BY COMBINING BETTER PHENOTYPING WITH PGX AND IMPROVED ANALYTICAL METHODS. THESE STRATEGIES CARRY THE DUAL BENEFIT OF DELIVERING DATA ON BIOMARKERS OF TREATMENT RESPONSE AS WELL AS POINTING TO DISEASE MECHANISMS THROUGH THE BIOLOGY OF THE MARKERS ASSOCIATED WITH RESPONSE. OVERALL, THESE EFFORTS CAN SERVE TO IDENTIFY CLINICAL, GENETIC, AND EPIGENETIC FACTORS THAT CAN BE INCORPORATED INTO A PHARMACO(EPI)GENETIC TEST THAT MAY ULTIMATELY IMPROVE TREATMENT RESPONSE AND REDUCE THE SOCIOECONOMIC BURDEN OF GAD. 2019 4 3606 36 IMPROVING TREATMENT OF NEURODEVELOPMENTAL DISORDERS: RECOMMENDATIONS BASED ON PRECLINICAL STUDIES. INTRODUCTION: NEURODEVELOPMENTAL DISORDERS (NDDS) ARE COMMON AND SEVERELY DEBILITATING. THEIR CHRONIC NATURE AND RELIANCE ON BOTH GENETIC AND ENVIRONMENTAL FACTORS MAKES STUDYING NDDS AND THEIR TREATMENT A CHALLENGING TASK. AREAS COVERED: HEREIN, THE AUTHORS DISCUSS THE NEUROBIOLOGICAL MECHANISMS OF NDDS, AND PRESENT RECOMMENDATIONS ON THEIR TRANSLATIONAL RESEARCH AND THERAPY, OUTLINED BY THE INTERNATIONAL STRESS AND BEHAVIOR SOCIETY. VARIOUS DRUGS CURRENTLY PRESCRIBED TO TREAT NDDS ALSO REPRESENT A HIGHLY DIVERSE GROUP. ACTING ON VARIOUS NEUROTRANSMITTER AND PHYSIOLOGICAL SYSTEMS, THESE DRUGS OFTEN LACK SPECIFICITY OF ACTION, AND ARE COMMONLY USED TO TREAT MULTIPLE OTHER PSYCHIATRIC CONDITIONS. THERE HAS ALSO BEEN RELATIVELY LITTLE PROGRESS IN THE DEVELOPMENT OF NOVEL MEDICATIONS TO TREAT NDDS. BASED ON CLINICAL, PRECLINICAL AND TRANSLATIONAL MODELS OF NDDS, OUR RECOMMENDATIONS COVER A WIDE RANGE OF METHODOLOGICAL APPROACHES AND CONCEPTUAL STRATEGIES. EXPERT OPINION: TO IMPROVE PHARMACOTHERAPY AND DRUG DISCOVERY FOR NDDS, WE NEED A STRONGER EMPHASIS ON TARGETING MULTIPLE ENDOPHENOTYPES, A BETTER DISSECTION OF GENETIC/EPIGENETIC FACTORS OR "HIDDEN HERITABILITY," AND A CAREFUL CONSIDERATION OF POTENTIAL DEVELOPMENTAL/TROPHIC ROLES OF BRAIN NEUROTRANSMITTERS. THE VALIDITY OF ANIMAL NDD MODELS CAN BE IMPROVED THROUGH DISCOVERY OF NOVEL (BEHAVIORAL, PHYSIOLOGICAL AND NEUROIMAGING) BIOMARKERS, APPLYING PROPER ENVIRONMENTAL ENRICHMENT, WIDENING THE SPECTRUM OF MODEL ORGANISMS, TARGETING DEVELOPMENTAL TRAJECTORIES OF NDD-RELATED BEHAVIORS AND COMORBID CONDITIONS BEYOND TRADITIONAL NDDS. WHILE THESE RECOMMENDATIONS CANNOT BE ADDRESSED ALL IN ONCE, OUR INCREASED UNDERSTANDING OF NDD PATHOBIOLOGY MAY TRIGGER INNOVATIVE CROSS-DISCIPLINARY RESEARCH EXPANDING BEYOND TRADITIONAL METHODS AND CONCEPTS. 2016 5 1160 31 CONTINUING WAR ON PAIN: A PERSONALIZED APPROACH TO THE THERAPY WITH NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AND OPIOIDS. SUCCESSFUL PAIN MANAGEMENT REQUIRES THE DELIVERY OF ANALGESIA WITH MINIMAL RISK OF ADVERSE DRUG REACTIONS. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AND OPIOIDS REMAIN THE MAINSTAY OF TREATMENT FOR THE MAJORITY OF PATIENTS. UNFORTUNATELY, ALMOST 50% OF ALL PATIENTS EXPERIENCE INADEQUATE PAIN RELIEF AND SERIOUS SIDE EFFECTS. ALLELIC VARIANTS IN GENES CODING FOR TARGET PROTEINS, TRANSPORTERS AND ENZYMES, WHICH GOVERN ANALGESIC DRUGS ACTION AND THEIR FATE IN THE ORGANISM, MIGHT EXPLAIN INTER-INDIVIDUAL VARIABILITY IN PAIN SEVERITY AND IN DRUG-INDUCED PAIN RELIEF AND TOXICITIES. ADDITIONALLY, IT SEEMS THAT EPIGENETIC CHANGES CONTRIBUTE TO THE HIGHLY VARIABLE RESPONSE TO PAIN TREATMENT. THEREFORE, PHARMACOGENOMIC TESTING MIGHT BE A VALUABLE TOOL FOR PERSONALIZATION OF PAIN TREATMENT, WITH A MULTIDISCIPLINARY TEAM APPROACH INVOLVED. 2019 6 8 36 'OMIC' GENETIC TECHNOLOGIES FOR HERBAL MEDICINES IN PSYCHIATRY. THE FIELD OF GENETICS, WHICH INCLUDES THE USE OF 'OMIC' TECHNOLOGIES, IS AN EVOLVING AREA OF SCIENCE THAT HAS EMERGING APPLICATION IN PHYTOTHERAPY. OMIC STUDIES INCLUDE PHARMACOGENOMICS, PROTEOMICS AND METABOLOMICS. HERBAL MEDICINES, AS MONOTHERAPIES, OR COMPLEX FORMULATIONS SUCH AS TRADITIONAL CHINESE HERBAL PRESCRIPTIONS, MAY BENEFIT FROM OMIC STUDIES, AND THIS NEW FIELD MAY BE TERMED 'HERBOMICS'. APPLYING HERBOMICS IN THE FIELD OF PSYCHIATRY MAY PROVIDE ANSWERS ABOUT WHICH HERBAL INTERVENTIONS MAY BE EFFECTIVE FOR INDIVIDUALS, WHICH GENETIC PROCESSES ARE TRIGGERED, AND THE SUBSEQUENT NEUROCHEMICAL PATHWAYS OF ACTIVITY. THE USE OF PROTEOMIC TECHNOLOGY CAN EXPLORE THE DIFFERING EPIGENETIC EFFECTS ON NEUROCHEMICAL GENE EXPRESSION BETWEEN INDIVIDUAL HERBS, ISOLATED CONSTITUENTS AND COMPLEX FORMULAE. THE POSSIBILITIES OF SIDE EFFECTS OR INSUFFICIENT RESPONSE TO THE HERB CAN ALSO BE ASSESSED VIA PHARMACOGENOMIC ANALYSIS OF POLYMORPHISMS OF CYTOCHROME P450 LIVER ENZYMES OR P-GLYCOPROTEIN. WHILE ANOTHER NOVEL APPLICATION OF OMIC TECHNOLOGY IS FOR THE VALIDATION OF THE CONCEPT OF SYNERGY IN INDIVIDUAL HERBAL EXTRACTS AND PRESCRIPTIVE FORMULATIONS. CHRONIC ADMINISTRATION OF PSYCHOTROPIC HERBAL MEDICINES MAY DISCOVER IMPORTANT EFFECTS ON CHROMATIN REMODELLING VIA MODIFICATION OF HISTONE AND DNA METHYLATION. THIS PAPER FOCUSES ON THE EMERGING FIELD OF HERBOMICS, AND IS TO OUR KNOWLEDGE THE FIRST PUBLICATION TO EXPLORE THIS IN THE AREA OF PSYCHIATRY. 2012 7 4532 30 MULTIMODAL ANALGESIA FOR PERIOPERATIVE MANAGEMENT OF PATIENTS PRESENTING FOR SPINAL SURGERY. MULTIMODAL, NON-OPIOID BASED ANALGESIA HAS BECOME THE CORNERSTONE OF ERAS PROTOCOLS FOR EFFECTIVE ANALGESIA AFTER SPINAL SURGERY. OPIOID SIDE EFFECTS, DEPENDENCE AND LEGISLATION RESTRICTING LONG TERM OPIOID USE HAS LED TO A RESURGENCE IN INTEREST IN OPIOID SPARING TECHNIQUES. THE INCREASING ARRAY OF MULTIMODAL OPIOID SPARING ANALGESICS AVAILABLE FOR SPINAL SURGERY TARGETING NOVEL RECEPTORS, TRANSMITTERS, AND ALTERING EPIGENETICS CAN HELP PROVIDE AN OPTIMAL PERIOPERATIVE EXPERIENCE WITH LESS OPIOID SIDE EFFECTS AND LONG-TERM DEPENDENCE. EPIGENETIC MECHANISMS OF PAIN MAY ENHANCE OR SUPPRESS GENE EXPRESSION, WITHOUT ALTERING THE GENOME ITSELF. SUCH MECHANISMS ARE COMPLEX, DYNAMIC AND RESPONSIVE TO ENVIRONMENT. ALTERATIONS THAT OCCUR CAN AFFECT THE PATHOPHYSIOLOGY OF PAIN MANAGEMENT AT A DNA LEVEL, MODIFYING PERCEIVED PAIN RELIEF. IN THIS REVIEW, WE PROVIDE A BRIEF OVERVIEW OF EPIGENETICS OF PAIN, SYSTEMIC LOCAL ANESTHETICS AND NEURAXIAL TECHNIQUES THAT CONTINUE TO REMAIN USEFUL FOR SPINAL SURGERY, NEUROPATHIC AGENTS, AS WELL AS OTHER COMMON AND LESS COMMON TARGET RECEPTORS FOR A TRULY MULTIMODAL APPROACH TO PERIOPERATIVE PAIN MANAGEMENT. 2019 8 6048 36 THE CONCEPTS OF ASTHMA ENDOTYPES AND PHENOTYPES TO GUIDE CURRENT AND NOVEL TREATMENT STRATEGIES. ASTHMA, A COMMON, NON-COMMUNICABLE CHRONIC DISEASE AFFECTS OVER 300 MILLION INDIVIDUALS WORLDWIDE. THE WESTERN WORLD LIFESTYLE IS CLAIMED TO BE RESPONSIBLE FOR THIS HIGH AND INCREASING PREVALENCE. ASTHMA HAS BEEN DEFINED AS A SYNDROME WITH VARIOUS PHENOTYPES AND ENDOTYPES, ALLERGIC ASTHMA AND TYPE 2 ASTHMA BEING THE MOST FREQUENT. A GREAT INCREASE IN PREVALENCE OF ALLERGIC DISEASES HAS NECESSITATED INTENSIVE INVESTIGATIONS BOTH FOR UNDERSTANDING THE UNDERLYING MECHANISMS AND FOR THE DEVELOPMENT OF NOVEL THERAPY OPTIONS WITH LONG-TERM EFFICACY AND LIMITED SIDE-EFFECTS. ALLERGIC PATIENTS DEMONSTRATE UNIQUE PRESENTATIONS WITH VARIABLE VISIBLE CHARACTERISTICS AND DISEASE OUTCOMES DEPENDING ON DIFFERENT MOLECULAR MECHANISMS, RELATED TO INFLUENCE OF GENES AND EPIGENETIC CONTROL BY MICRO- AND MACRO-ENVIRONMENT. AREAS COVERED: THIS ARTICLE REVIEWS THE DEFINITION OF ASTHMA PHENOTYPES AND POSSIBLE ENDOTYPES, ADVANCES IN ALLERGY-IMMUNOLOGY FIELD AND CONTEMPORARY PERSONALIZED THERAPY OPTIONS FOR ASTHMA. EXPERT COMMENTARY: BETTER UNDERSTANDING OF THE COMPLEX IMMUNE NETWORK OF ALLERGIC INFLAMMATION AND KEY PLAYERS OF IMMUNITY IS CONTINUOUSLY BEING PROVIDED FOR CLARIFICATION OF ASTHMA SUB-TYPES. SUCCESSFUL THERAPY OF ASTHMA REQUIRES BETTER DEFINITION OF UNDERLYING PATHOGENESIS, WHICH SEQUENTIALLY COULD END UP WITH 'CUSTOM-TAILORED' INDIVIDUALIZED, EVIDENCE-BASED AND MORE PRECISE THERAPY OPTIONS; A NEW ERA TERMED AS 'PRECISION MEDICINE'. ENDOTYPE, PHENOTYPE, THERATYPE AND BIOMARKER TERMS ARISE AS MAJOR KEYWORDS IN PRECISION/PERSONALIZED MEDICINE. 2018 9 5163 34 PRECISION/PERSONALIZED MEDICINE IN ALLERGIC DISEASES AND ASTHMA. LIKE MANY OTHER CHRONIC DISEASES, EVERY ALLERGIC PATIENT HAS DIFFERENT CHARACTERISTICS BASED ON CLINICAL COURSE, TREATMENT RESPONSIVENESS AND DISEASE OUTCOMES, WHICH ARE ASSOCIATED WITH THE GENETIC AND EPIGENETIC CONTROL OF MOLECULAR MECHANISMS AND ENVIRONMENT. THIS VARIABILITY NECESSITATES THE ESTABLISHMENT OF PATIENT-TAILORED AND PRECISION APPROACHES IN HANDLING ALLERGIC DISORDERS. BETTER UNDERSTANDING OF THE UNDERLYING PATHOPHYSIOLOGICAL MECHANISMS FOR THE DEVELOPMENT OF ALLERGIC DISORDERS WILL PROVIDE MORE RATIONALE STRATEGIES BASED ON INDIVIDUAL CASES IN CONTROLLING AND TREATING THESE DISORDERS. ENDOTYPING, PHENOTYPING, GENOTYPING AND THERATYPING, AND BIOMARKERS ARE KEYWORDS IN THIS AREA AND HAVE BEEN GAINING LOTS OF ATTENTION IN THE FIELD OF PRECISION MEDICINE, WHICH AIMS TO REVOLUTIONIZE PATIENT CARE AND DEVELOP BETTER PREVENTION AND TREATMENT STRATEGIES. IN ADDITION, PRECISION HEALTH IS A NEW CONCEPT THAT BRINGS PRECISE APPROACHES TO THE SCENE FOR BEING HEALTHY AND PREVENTION OF ALLERGIC DISEASE AND ASTHMA. THE SPECIALTY OF ALLERGY HAS A LEADING ROLE IN THE FIELD, BECAUSE ALLERGEN-SPECIFIC IMMUNOTHERAPY STARTED 105 YEARS AGO, AND IS HISTORICALLY A LEADING PERSONALIZED/PRECISION MEDICINE APPROACH IN ALL MEDICINE DISCIPLINES PROVIDING THE POSSIBILITY OF CURE IN AN INDIVIDUALIZED MANNER INSTEAD OF CONVENTIONAL SYMPTOMATIC TREATMENTS. 2018 10 5039 40 PHARMACOGENETICS OF CHRONIC PAIN MANAGEMENT. OBJECTIVE: THE EXPERIENCE OF CHRONIC PAIN IS ONE OF THE COMMONEST REASONS INDIVIDUALS SEEK MEDICAL ATTENTION, MAKING THE MANAGEMENT OF CHRONIC PAIN A MAJOR ISSUE IN CLINICAL PRACTICE. DRUG METABOLISM AND RESPONSES ARE AFFECTED BY MANY FACTORS, WITH GENETIC VARIATIONS OFFERING ONLY A PARTIAL EXPLANATION OF AN INDIVIDUAL'S RESPONSE. THERE IS A PAUCITY OF EVIDENCE FOR THE BENEFITS OF PHARMACOGENETIC TESTING IN THE CONTEXT OF PAIN MANAGEMENT. DESIGN AND METHODS: WE REVIEWED THE LITERATURE BETWEEN 2000 AND 2013, AND REFERENCES CITED THEREIN, USING VARIOUS KEYWORDS RELATED TO PAIN MANAGEMENT, PHARMACOLOGY AND PHARMACOGENETICS. RESULTS: OPIOIDS CONTINUE TO BE THE MAINSTAY OF CHRONIC PAIN MANAGEMENT. SEVERAL NON-OPIOID BASED THERAPIES, SUCH AS TREATMENT WITH CANNABINOIDS, GENE THERAPY AND EPIGENETIC-BASED APPROACHES ARE NOW AVAILABLE FOR THESE PATIENTS. ADJUVANT THERAPIES WITH ANTIDEPRESSANTS, BENZODIAZEPINES OR ANTICONVULSANTS CAN ALSO BE USEFUL IN MANAGING PAIN. CURRENTLY, LABORATORY MONITORING OF PAIN MANAGEMENT PATIENTS, IF PERFORMED, IS LARGELY THROUGH URINE DRUG MEASUREMENTS. CONCLUSIONS: DRUG HALF-LIFE CALCULATIONS CAN BE USED AS FUNCTIONAL MARKERS OF THE CUMULATIVE EFFECT OF PHARMACOGENETICS AND DRUG-DRUG INTERACTIONS. ASSESSMENT OF HALF-LIFE AND THERAPEUTIC EFFECTS MAY BE MORE USEFUL THAN GENETIC TESTING IN PREVENTING ADVERSE DRUG REACTIONS TO PAIN MEDICATIONS, WHILE ENSURING EFFECTIVE ANALGESIA. DEFINITIVE, MASS SPECTROMETRY-BASED METHODS, CAPABLE OF MEASURING PARENT DRUG AND METABOLITE LEVELS, ARE THE MOST USEFUL ASSAYS FOR THIS PURPOSE. URINE DRUG MEASUREMENTS DO NOT NECESSARILY CORRELATE WITH SERUM DRUG CONCENTRATIONS OR THERAPEUTIC EFFECTS. THEREFORE, THEY ARE LIMITED IN THEIR USE IN MONITORING EFFICACY AND TOXICITY. 2014 11 6776 30 [APPROACHING NEW PHARMACOTHERAPY OPTIONS IN PAIN TREATMENT]. THE EVOLUTION OF MEDICINE IS NOTICEABLE IN MOST THERAPEUTIC AREAS, THE WORSE THE CURRENT THERAPEUTIC RESULT, THE MORE QUICK THE IMPROVEMENT. THIS IS ESPECIALLY TRUE IN SUCH AREAS THAT REQUIRE SUBSTANTIAL SOCIAL RESOURCES, NAMELY ONCOLOGY, DIABETOLOGY AND CNS DISEASES. PAIN IS NOT A DISEASE, IT IS A SYMPTOM. PAIN IS ONE OF THE MOST IMPORTANT COMPONENTS OF HUMAN SUFFERING THUS IT DESERVES SPECIAL ATTENTION. IN RECENT YEARS NEW FORMULATIONS OF OLD MEDICINES WERE INTRODUCED RATHER THAN NEW MEDICINES. MAYBE ZICONITIDE IS THE LAST PAIN KILLER WITH NEW MECHANISM OF ACTION WHICH WAS APPROVED BY FDA IN 2004. HOWEVER, THE NEW INFORMATION AND TECHNIQUES ARE ALSO APPEARING IN THE FIELD OF ANALGESIA. NOWADAYS ONE CAN TALK ABOUT GENETIC/EPIGENETIC TARGETS, RNA THERAPIES, VOLTAGE-GATED CALCIUM CHANNELS, NEW PAIN RECEPTORS (TRPV1, TRPV4, NMDA, NAV RECEPTORS) REGARDING PAIN TREATMENT, INDICATING THAT THE PRACTICE OF THE PHARMACOTHERAPY OF PAIN WILL CHANGE FUNDAMENTALLY IN THE IMMEDIATE FUTURE. THIS PAPER IS INTENDED TO GIVE A SHORT SUMMARY OF THESE NEW OPTIONS. 2017 12 5025 41 PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS. PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS (CVD), ALSO REFERRED TO AS PERSONALIZED OR PRECISION CARDIOLOGY IN ACCORDANCE WITH GENERAL PRINCIPLES OF PERSONALIZED MEDICINE, IS SELECTION OF THE BEST TREATMENT FOR AN INDIVIDUAL PATIENT. IT INVOLVES THE INTEGRATION OF VARIOUS "OMICS" TECHNOLOGIES SUCH AS GENOMICS AND PROTEOMICS AS WELL AS OTHER NEW TECHNOLOGIES SUCH AS NANOBIOTECHNOLOGY. MOLECULAR DIAGNOSTICS AND BIOMARKERS ARE IMPORTANT FOR LINKING DIAGNOSIS WITH THERAPY AND MONITORING THERAPY. BECAUSE CVD INVOLVE PERTURBATIONS OF LARGE COMPLEX BIOLOGICAL NETWORKS, A SYSTEMS BIOLOGY APPROACH TO CVD RISK STRATIFICATION MAY BE USED FOR IMPROVING RISK-ESTIMATING ALGORITHMS, AND MODELING OF PERSONALIZED BENEFIT OF TREATMENT MAY BE HELPFUL FOR GUIDING THE CHOICE OF INTERVENTION. BIOINFORMATICS TOOLS ARE HELPFUL IN ANALYZING AND INTEGRATING LARGE AMOUNTS OF DATA FROM VARIOUS SOURCES. PERSONALIZED THERAPY IS CONSIDERED DURING DRUG DEVELOPMENT, INCLUDING METHODS OF TARGETED DRUG DELIVERY AND CLINICAL TRIALS. INDIVIDUALIZED RECOMMENDATIONS CONSIDER MULTIPLE FACTORS - GENETIC AS WELL AS EPIGENETIC - FOR PATIENTS' RISK OF HEART DISEASE. EXAMPLES OF PERSONALIZED TREATMENT ARE THOSE OF CHRONIC MYOCARDIAL ISCHEMIA, HEART FAILURE, AND HYPERTENSION. SIMILAR APPROACHES CAN BE USED FOR THE MANAGEMENT OF ATRIAL FIBRILLATION AND HYPERCHOLESTEROLEMIA, AS WELL AS THE USE OF ANTICOAGULANTS. PERSONALIZED MANAGEMENT INCLUDES PHARMACOTHERAPY, SURGERY, LIFESTYLE MODIFICATIONS, AND COMBINATIONS THEREOF. FURTHER PROGRESS IN UNDERSTANDING THE PATHOMECHANISM OF COMPLEX CARDIOVASCULAR DISEASES AND IDENTIFICATION OF CAUSATIVE FACTORS AT THE INDIVIDUAL PATIENT LEVEL WILL PROVIDE OPPORTUNITIES FOR THE DEVELOPMENT OF PERSONALIZED CARDIOLOGY. APPLICATION OF PRINCIPLES OF PERSONALIZED MEDICINE WILL IMPROVE THE CARE OF THE PATIENTS WITH CVD. 2017 13 1037 20 CLASSIFICATION AND DIAGNOSIS OF TEMPOROMANDIBULAR DISORDERS AND TEMPOROMANDIBULAR DISORDER PAIN. DESIGNING CLASSIFICATION SYSTEMS AND DEVELOPING DIAGNOSTIC CRITERIA FOR TEMPOROMANDIBULAR DISORDERS IS DIFFICULT. AN APPRECIATION OF THE UTILITY AND APPLICABILITY OF THESE ENTITIES REQUIRES AN UNDERSTANDING OF THE IMPORTANCE OF EACH, THE DIFFERENCES BETWEEN THE TWO, AND HOW THEY MAY BE OPTIMALLY OPERATIONALIZED FOR BOTH CLINICAL AND RESEARCH ACTIVITIES IN LIGHT OF THEIR INHERENT ADVANTAGES AND LIMITATIONS. IN ADDITION, CONSIDERATION FOR ADOPTING NEWER APPROACHES, SUCH AS FOLLOWING ONTOLOGICAL AND PRECISION-BASED MEDICINE PRINCIPLES, ACCOUNTING FOR GENETICS/EPIGENETIC AND NEUROBIOLOGICAL FACTORS, AND THE INCLUSION OF BIOMARKERS WILL POTENTIALLY RESULT IN MORE THOROUGH AND COMPREHENSIVE CLASSIFICATION SYSTEMS AND DIAGNOSTIC CRITERIA. 2023 14 5028 35 PERSONALIZING PEDIATRIC PAIN MEDICINE: USING POPULATION-SPECIFIC PHARMACOGENETICS, GENOMICS, AND OTHER -OMICS APPROACHES TO PREDICT RESPONSE. PERSONALIZED MEDICINE IS THE SCIENCE OF INDIVIDUALIZED PREVENTION AND THERAPY. THE NOTION THAT "ONE SIZE FITS ALL" HAS BEEN REPLACED BY THE IDEA OF PATIENT-TAILORED HEALTH CARE. WITHIN THIS PARADIGM, THE RESEARCH COMMUNITY HAS TURNED TO EXAMINE GENETIC PREDICTORS OF DISEASE AND TREATMENT RESPONSES. PAIN RESEARCHERS HAVE PRODUCED GENETIC STUDIES OVER THE LAST DECADE THAT EVALUATE THE ASSOCIATION OF GENETIC VARIABILITY WITH PAIN SENSITIVITY AND ANALGESIC RESPONSE. WHILE MOST OF THESE STUDIES HAVE BEEN CONDUCTED AMONG COHORTS OF SUBJECTS OF EUROPEAN DESCENT, SOME HAVE INCLUDED OTHER RACIAL AND ETHNIC GROUPS, PROVIDING EVIDENCE OF VARIABLE RESPONSES TO ANALGESICS. SIMULTANEOUSLY, THERE IS AN INCREASED RECOGNITION REGARDING THE COMPLEXITY OF PAIN RESEARCH, ACKNOWLEDGING THE ADDITIONAL ROLE OF EPIGENETIC, TRANSCRIPTOMIC, PROTEOMIC, AND METABOLOMIC FACTORS IN THE DEVELOPMENT, EXPERIENCE, AND TREATMENT OF PAIN. THIS ARTICLE PROVIDES AN INTRODUCTION TO POPULATION-SPECIFIC PHARMACOGENETICS, PROTEOMICS AND OTHER "-OMICS" TECHNOLOGIES TO PREDICT DRUG RESPONSE TO PAIN MEDICATIONS IN CHILDREN. IT AIMS TO PROVIDE ANESTHESIOLOGISTS WITH THE BASIC KNOWLEDGE TO UNDERSTAND THE POTENTIAL IMPLICATIONS OF GENETIC AND EPIGENETIC FACTORS MANAGING THE PAIN OF PEDIATRIC PATIENTS. 2015 15 4518 27 MULTI-OMICS FOR BIOMARKER APPROACHES IN THE DIAGNOSTIC EVALUATION AND MANAGEMENT OF ABDOMINAL PAIN AND IRRITABLE BOWEL SYNDROME: WHAT LIES AHEAD. RELIABLE BIOMARKERS FOR COMMON DISORDERS OF GUT-BRAIN INTERACTION CHARACTERIZED BY ABDOMINAL PAIN, INCLUDING IRRITABLE BOWEL SYNDROME (IBS), ARE CRITICALLY NEEDED TO ENHANCE CARE AND DEVELOP INDIVIDUALIZED THERAPIES. THE DYNAMIC AND HETEROGENEOUS NATURE OF THE PATHOPHYSIOLOGICAL MECHANISMS THAT UNDERLIE VISCERAL HYPERSENSITIVITY HAVE CHALLENGED SUCCESSFUL BIOMARKER DEVELOPMENT. CONSEQUENTLY, EFFECTIVE THERAPIES FOR PAIN IN IBS ARE LACKING. HOWEVER, RECENT ADVANCES IN MODERN OMICS TECHNOLOGIES OFFER NEW OPPORTUNITIES TO ACQUIRE DEEP BIOLOGICAL INSIGHTS INTO MECHANISMS OF PAIN AND NOCICEPTION. NEWER METHODS FOR LARGE-SCALE DATA INTEGRATION OF COMPLEMENTARY OMICS APPROACHES HAVE FURTHER EXPANDED OUR ABILITY TO BUILD A HOLISTIC UNDERSTANDING OF COMPLEX BIOLOGICAL NETWORKS AND THEIR CO-CONTRIBUTIONS TO ABDOMINAL PAIN. HERE, WE REVIEW THE MECHANISMS OF VISCERAL HYPERSENSITIVITY, FOCUSING ON IBS. WE DISCUSS CANDIDATE BIOMARKERS FOR PAIN IN IBS IDENTIFIED THROUGH SINGLE OMICS STUDIES AND SUMMARIZE EMERGING MULTI-OMICS APPROACHES FOR DEVELOPING NOVEL BIOMARKERS THAT MAY TRANSFORM CLINICAL CARE FOR PATIENTS WITH IBS AND ABDOMINAL PAIN. 2023 16 1984 29 EPIGENETIC ALTERATIONS IN PRESCRIPTION OPIOID MISUSE: NEW STRATEGIES FOR PRECISION PAIN MANAGEMENT. PRESCRIPTION OPIOIDS ARE USED FOR SOME CHRONIC PAIN CONDITIONS. HOWEVER, GENERALLY, LONG-TERM THERAPY HAS UNWANTED SIDE EFFECTS WHICH MAY TRIGGER ADDICTION, OVERDOSE, AND EVENTUALLY CAUSE DEATHS. OPIOID ADDICTION AND CHRONIC PAIN CONDITIONS HAVE BOTH BEEN ASSOCIATED WITH EVIDENCE OF GENETIC AND EPIGENETIC ALTERATIONS. DESPITE INTENSE RESEARCH INTEREST, MANY QUESTIONS ABOUT THE CONTRIBUTION OF EPIGENETIC CHANGES TO THIS TYPOLOGY OF ADDICTION VULNERABILITY AND DEVELOPMENT REMAIN UNANSWERED. THE AIM OF THIS REVIEW WAS TO SUMMARIZE THE EPIGENETIC MODIFICATIONS DETECTED IN SPECIFIC TISSUES OR BRAIN AREAS AND ASSOCIATED WITH OPIOID PRESCRIPTION AND MISUSE IN PATIENTS WHO HAVE INITIATED PRESCRIBED OPIOID MANAGEMENT FOR CHRONIC NON-CANCER PAIN. THE REVIEW CONSIDERS THE EFFECTS OF OPIOID EXPOSURE ON THE EPIGENOME IN CENTRAL AND PERIPHERAL TISSUES IN ANIMAL MODELS AND HUMAN SUBJECTS AND HIGHLIGHTS THE MECHANISMS IN WHICH OPIOID EPIGENETICS MAY BE INVOLVED. THIS WILL IMPROVE OUR CURRENT UNDERSTANDING, PROVIDE THE BASIS FOR TARGETED, PERSONALIZED PAIN MANAGEMENT, AND THUS BALANCE OPIOID RISKS AND BENEFITS IN MANAGING CHRONIC PAIN. 2021 17 367 32 AMPLIFIED PAIN SYNDROMES IN CHILDREN: TREATMENT AND NEW INSIGHTS INTO DISEASE PATHOGENESIS. PURPOSE OF REVIEW: ALTHOUGH MANY DIAGNOSTIC TERMS ARE USED FOR PEDIATRIC CHRONIC PAIN, EVIDENCE SUGGESTS A COMMON THREAD OF SIGNAL AMPLIFICATION, LEADING TO THE UNIFYING TERM 'AMPLIFIED PAIN SYNDROMES'. ONGOING RESEARCH PROVIDES NEW INSIGHTS INTO BIOPSYCHOSOCIAL CONTRIBUTORS AND TREATMENTS FOR PEDIATRIC AMPLIFIED PAIN SYNDROMES. RECENT FINDINGS: BASIC SCIENCE INDICATES A COMPLEX INTERPLAY OF GENETIC, EPIGENETIC, NEUROCHEMICAL, ENDOCRINE, AND INFLAMMATORY CONTRIBUTORS, ALONG WITH ENVIRONMENTAL AND PSYCHOLOGICAL FACTORS. ALTHOUGH MEDICATIONS AND INTERVENTIONS REMAIN COMMON APPROACHES TO CHILDREN WITH CHRONIC PAIN, THEIR EVIDENCE IS LIMITED. PRELIMINARY EVIDENCE EXISTS FOR MINDFULNESS-BASED THERAPIES, YOGA, AND OTHER COMPLEMENTARY/ALTERNATIVE MEDICINE APPROACHES. THE STRONGEST EVIDENCE IS FOR EXERCISE-BASED AND COGNITIVE-BEHAVIORAL TREATMENTS, IN PARTICULAR, WHEN COMBINED IN A MULTIDISCIPLINARY FORMAT. INTENSIVE APPROACHES (PAIN REHABILITATION) HAVE THE POTENTIAL TO EFFECTIVELY AND EFFICIENTLY TREAT THOSE MOST DISABLED BY AMPLIFIED PAIN SYNDROMES, AND LEAD TO SUSTAINED IMPROVEMENT IN PAIN, FUNCTIONING, AND MEDICAL UTILIZATION. SUMMARY: ALTHOUGH UNDERSTANDING OF THE MECHANISMS UNDERLYING PEDIATRIC AMPLIFIED PAIN SYNDROMES EVOLVES, STANDARD OF CARE IS MULTIDISCIPLINARY EMPHASIZING EXERCISE THERAPY, COGNITIVE-BEHAVIORAL TREATMENT, AND SELF-REGULATION. TREATMENT SHOULD TARGET FULL RETURN TO PHYSICAL FUNCTION, WHICH LEADS TO SUBSEQUENT IMPROVEMENT OR RESOLUTION OF PAIN. MULTIDISCIPLINARY CARE CAN BE COORDINATED BY A RHEUMATOLOGIST OR OTHER PHYSICIAN WITH APPROPRIATE REFERRALS, OR THROUGH A MULTIDISCIPLINARY TEAM. 2014 18 6617 36 UNDERPINNING THE NEUROBIOLOGICAL INTRICACIES ASSOCIATED WITH OPIOID TOLERANCE. THE OPIOID CRISIS IS A MAJOR THREAT OF THE 21ST CENTURY, WITH A REMARKABLE JUXTAPOSITION OF USE AND ABUSE. OPIOIDS ARE THE MOST POTENT AND EFFICACIOUS CLASS OF ANALGESICS, BUT DESPITE THEIR PROVEN THERAPEUTIC EFFICACY, THEY HAVE RECENTLY BEEN DEGRADED TO THIRD-LINE THERAPY FOR THE MANAGEMENT OF CHRONIC PAIN IN CLINICS. THE REASON BEHIND THIS IS THE DEVELOPMENT OF POTENTIAL SIDE EFFECTS AND TOLERANCE AFTER REPEATED DOSING. OPIOID TOLERANCE IS THE MAJOR LIMITING FACTOR LEADING TO THE WITHDRAWAL OF TREATMENT, SEVERE SIDE EFFECTS DUE TO DOSE ESCALATION, AND SOMETIMES EVEN DEATH OF THE PATIENTS. EVERY DAY MORE THAN 90 PEOPLE DIE DUE TO OPIOIDS OVERDOSE IN AMERICA, AND A SIMILAR TREND HAS BEEN SEEN ACROSS THE GLOBE. OVER THE PAST TWO DECADES, RESEARCHERS HAVE BEEN TRYING TO DISSECT THE NEUROBIOLOGICAL MECHANISM OF OPIOID TOLERANCE. RESEARCH ON OPIOID TOLERANCE SHIFTED TOWARD CENTRAL NERVOUS SYSTEM-BASED ADAPTATIONS BECAUSE TOLERANCE IS MUCH MORE THAN JUST A CELLULAR PHENOMENON. THUS, NEUROBIOLOGICAL ADAPTATIONS ASSOCIATED WITH OPIOID TOLERANCE ARE IMPORTANT TO UNDERSTAND IN ORDER TO FIND NEWER PAIN THERAPEUTICS. THESE ADAPTATIONS ARE ASSOCIATED WITH ALTERATIONS IN ASCENDING AND DESCENDING PAIN PATHWAYS, REWARD CIRCUITRY MODULATIONS, RECEPTOR DESENSITIZATION AND DOWN-REGULATION, RECEPTOR INTERNALIZATION, HETERODIMERIZATION, AND ALTERED EPIGENETIC REGULATION. THE PRESENT REVIEW IS FOCUSED ON NOVEL CIRCUITRIES ASSOCIATED WITH OPIOID TOLERANCE IN DIFFERENT AREAS OF THE BRAIN, SUCH AS PERIAQUEDUCTAL GRAY, ROSTRAL VENTROMEDIAL MEDULLA, DORSAL RAPHE NUCLEUS, VENTRAL TEGMENTAL AREA, AND NUCLEUS ACCUMBENS. UNDERSTANDING THE NEUROBIOLOGICAL MODULATIONS ASSOCIATED WITH CHRONIC OPIOID EXPOSURE AND TOLERANCE WILL PAVE THE WAY FOR THE DEVELOPMENT OF NOVEL PHARMACOLOGICAL TOOLS FOR SAFER AND BETTER MANAGEMENT OF CHRONIC PAIN IN PATIENTS. 2020 19 103 38 A REHABILOMICS FRAMEWORK FOR PERSONALIZED AND TRANSLATIONAL REHABILITATION RESEARCH AND CARE FOR INDIVIDUALS WITH DISABILITIES: PERSPECTIVES AND CONSIDERATIONS FOR SPINAL CORD INJURY. DESPITE MANY PEOPLE HAVING SIMILAR CLINICAL PRESENTATION, DEMOGRAPHIC FACTORS, AND CLINICAL CARE, OUTCOME CAN DIFFER FOR THOSE SUSTAINING SIGNIFICANT INJURY SUCH AS SPINAL CORD INJURY (SCI) AND TRAUMATIC BRAIN INJURY (TBI). IN ADDITION TO TRADITIONAL DEMOGRAPHIC, SOCIAL, AND CLINICAL FACTORS, VARIABILITY ALSO MAY BE ATTRIBUTABLE TO INNATE (INCLUDING GENETIC, TRANSCRIPTOMIC PROTEOMIC, EPIGENETIC) BIOLOGICAL VARIATION THAT INDIVIDUALS BRING TO RECOVERY AND THEIR UNIQUE RESPONSE TO THEIR CARE AND ENVIRONMENT. TECHNOLOGIES COLLECTIVELY CALLED "-OMICS" ENABLE SIMULTANEOUS MEASUREMENT OF AN ENORMOUS NUMBER OF BIOMOLECULES THAT CAN CAPTURE MANY POTENTIAL BIOLOGICAL CONTRIBUTORS TO HETEROGENEITY OF INJURY/DISEASE COURSE AND OUTCOME. DUE TO THE NATURE OF INJURY AND COMPLEX DISEASE, AND ITS ASSOCIATIONS WITH IMPAIRMENT, DISABILITY, AND RECOVERY, REHABILITATION DOES NOT LEND ITSELF TO A SINGULAR "PROTOCOLIZED" PLAN OF THERAPY. YET, BY NATURE AND BY NECESSITY, REHABILITATION MEDICINE OPERATES AS A FUNCTIONAL MODEL OF "PERSONALIZED CARE". THUS, THE CHALLENGE FOR SUCCESSFUL PROGRAMS OF TRANSLATIONAL REHABILITATION CARE AND RESEARCH IS TO IDENTIFY VIABLE APPROACHES TO EXAMINE BROAD POPULATIONS, WITH VARIED IMPAIRMENTS AND FUNCTIONAL LIMITATIONS, AND TO IDENTIFY EFFECTIVE TREATMENT RESPONSES THAT INCORPORATE PERSONALIZED PROTOCOLS TO OPTIMIZE FUNCTIONAL RECOVERY. THE REHABILOMICS FRAMEWORK IS A TRANSLATIONAL MODEL THAT PROVIDES AN "-OMICS" OVERLAY TO THE SCIENTIFIC STUDY OF REHABILITATION PROCESSES AND MULTIDIMENSIONAL OUTCOMES. REHABILOMICS RESEARCH PROVIDES NOVEL OPPORTUNITIES TO EVALUATE THE NEUROBIOLOGY OF COMPLEX INJURY OR CHRONIC DISEASE AND CAN BE USED TO EXAMINE METHODS AND TREATMENTS FOR PERSON-CENTERED CARE AMONG POPULATIONS WITH DISABILITIES. EXEMPLARS FOR APPLICATION IN SCI AND OTHER NEUROREHABILITATION POPULATIONS ARE DISCUSSED. 2014 20 4515 39 MULTI-OMICS APPROACHES FOR PRECISION OBESITY MANAGEMENT : POTENTIALS AND LIMITATIONS OF OMICS IN PRECISION PREVENTION, TREATMENT AND RISK REDUCTION OF OBESITY. INTRODUCTION: OBESITY IS A MULTIFACTORIAL CHRONIC DISEASE THAT CANNOT BE ADDRESSED BY SIMPLY PROMOTING BETTER DIETS AND MORE PHYSICAL ACTIVITY. TO DATE, NOT A SINGLE COUNTRY HAS SUCCESSFULLY BEEN ABLE TO CURB THE ACCUMULATING BURDEN OF OBESITY. ONE EXPLANATION FOR THE LACK OF PROGRESS IS THAT LIFESTYLE INTERVENTION PROGRAMS ARE TRADITIONALLY IMPLEMENTED WITHOUT A COMPREHENSIVE EVALUATION OF AN INDIVIDUAL'S DIAGNOSTIC BIOMARKERS. EVIDENCE FROM GENOME-WIDE ASSOCIATION STUDIES HIGHLIGHT THE IMPORTANCE OF GENETIC AND EPIGENETIC FACTORS IN THE DEVELOPMENT OF OBESITY AND HOW THEY IN TURN AFFECT THE TRANSCRIPTOME, METABOLITES, MICROBIOMES, AND PROTEOMES. OBJECTIVE: THE PURPOSE OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF THE DIFFERENT TYPES OF OMICS DATA: GENOMICS, EPIGENOMICS, TRANSCRIPTOMICS, PROTEOMICS, METABOLOMICS AND ILLUSTRATE HOW A MULTI-OMICS APPROACH CAN BE FUNDAMENTAL FOR THE IMPLEMENTATION OF PRECISION OBESITY MANAGEMENT. RESULTS: THE DIFFERENT TYPES OF OMICS DESIGNS ARE GROUPED INTO TWO CATEGORIES, THE GENOTYPE APPROACH AND THE PHENOTYPE APPROACH. WHEN APPLIED TO OBESITY PREVENTION AND MANAGEMENT, EACH OMICS TYPE COULD POTENTIALLY HELP TO DETECT SPECIFIC BIOMARKERS IN PEOPLE WITH RISK PROFILES AND GUIDE HEALTHCARE PROFESSIONALS AND DECISION MAKERS IN DEVELOPING INDIVIDUALIZED TREATMENT PLANS ACCORDING TO THE NEEDS OF THE INDIVIDUAL BEFORE THE ONSET OF OBESITY. CONCLUSION: INTEGRATING MULTI-OMICS APPROACHES WILL ENABLE A PARADIGM SHIFT FROM THE ONE SIZE FITS ALL APPROACH TOWARDS PRECISION OBESITY MANAGEMENT, I.E. (1) PRECISION PREVENTION OF THE ONSET OF OBESITY, (2) PRECISION MEDICINE AND TAILORED TREATMENT OF OBESITY, AND (3) PRECISION RISK REDUCTION AND PREVENTION OF SECONDARY DISEASES RELATED TO OBESITY. 2023