1 3280 125 HERPES ZOSTER OPHTHALMICUS FOLLOWING ONABOTULINUMTOXINA ADMINISTRATION FOR CHRONIC MIGRAINE: A CASE REPORT AND LITERATURE REVIEW. BACKGROUND: THERE IS A GROWING BODY OF LITERATURE DOCUMENTING LOCAL HERPES ZOSTER OUTBREAK FOLLOWING PROCEDURES. THE MECHANISM UNDERLYING THESE OUTBREAKS REMAINS ELUSIVE. WE PRESENT A CASE OF ZOSTER FOLLOWING ONABOTULINUMTOXINA (BTX) FOR MIGRAINE AND A LITERATURE REVIEW. METHODS: CHART AND LITERATURE REVIEW. CASE: A 72-YEAR-OLD WOMAN WITH CHRONIC MIGRAINE RECEIVED BTX INJECTIONS FOR 3 YEARS WITHOUT INCIDENT. SHE HAD A HISTORY OF THORACIC ZOSTER WITH SUBSEQUENT POST-HERPETIC NEURALGIA. IN AUGUST 2013, 48 HOURS AFTER RECEIVING BTX INJECTIONS, SHE DEVELOPED A PAINFUL RASH IN THE RIGHT V1 DISTRIBUTION CONSISTENT WITH HERPES ZOSTER OPHTHALMICUS. ONE WEEK LATER THE RASH HAD RESOLVED WITHOUT TREATMENT. LITERATURE REVIEW: WE IDENTIFIED 65 (INCLUDING 2 FROM JUEL-JENSON) CASES OF ZOSTER REACTIVATION FOLLOWING MINOR PROCEDURES. THESE CASES TEND TO BE IN YOUNG PATIENTS WITHOUT SPECIFIC RISK FACTORS. OUTBREAKS CHARACTERISTICALLY OCCUR AT THE LEVEL OF EXPOSURE TO LOCAL TRAUMA. DISCUSSION: OUR REVIEW SUGGESTS THAT LOCAL TRAUMA, REGARDLESS OF THE NATURE OF STIMULI, MAY BE SUFFICIENT FOR ZOSTER REACTIVATION. WE HYPOTHESIZE THAT THE STRESSORS IN THESE REPORTED CASES EXERT A LOCAL EPIGENETIC INFLUENCE ON VIRAL TRANSCRIPTION, ALLOWING FOR VIRAL REACTIVATION. CONCLUSION: ZOSTER IS A POTENTIAL COMPLICATION OF BTX ADMINISTRATION FOR CHRONIC MIGRAINE IN ADULTS. PHYSICIAN AWARENESS CAN REDUCE THE SIGNIFICANT MORBIDITY ASSOCIATED WITH THIS DISEASE. 2015 2 6159 28 THE GENETICS AND EPIGENETICS OF FATIGUE. FATIGUE IS A COMMON SYMPTOM AND INCLUDES BOTH PHYSICAL AND MENTAL COMPONENTS. IT CAN BE ASSOCIATED WITH A VARIETY OF DIFFERENT SYNDROMES AND DISEASES, BUT IN MANY CASES IS NOT ASSOCIATED WITH OTHER COMORBID CONDITIONS. MOST HUMANS HAVE EXPERIENCED ACUTE FATIGUE IN RELATION TO DIFFERENT STRESSORS. ACUTE FATIGUE TYPICALLY DECREASES AS THE EFFECT OF THE TRIGGERING FACTOR IS REDUCED AND A NORMAL HOMEOSTATIC BALANCE IS RESTORED. FATIGUE THAT PERSISTS FOR 6 MONTHS OR MORE IS TERMED CHRONIC FATIGUE. CHRONIC FATIGUE (CF) IN COMBINATION WITH A MINIMUM OF 4 OF 8 SYMPTOMS AND THE ABSENCE OF DISEASES THAT COULD EXPLAIN THESE SYMPTOMS, CONSTITUTE THE CASE DEFINITION FOR CHRONIC FATIGUE SYNDROME. IN SPITE OF ITS PREVALENCE, THE BIOLOGY OF FATIGUE IS RELATIVELY POORLY UNDERSTOOD AND BIOLOGICAL MARKERS HAVE NOT YET BEEN IDENTIFIED. THIS LITERATURE SEARCH WAS PERFORMED IN PUBMED TO IDENTIFY RESEARCH ON THE GENETICS AND EPIGENETICS OF FATIGUE. PUBLICATIONS WERE INCLUDED IF FATIGUE WAS A MAJOR TOPIC AND THE TOPIC WAS COMBINED WITH GENETIC AND/OR EPIGENETIC MEASUREMENTS IN ADULT HUMANS. A TOTAL OF 40 PUBLICATIONS WERE IDENTIFIED. ALTHOUGH ALTERED FUNCTIONING IN THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS, THE SEROTONERGIC SYSTEM, AND ASSOCIATIONS WITH INFECTIOUS AGENTS HAVE BEEN IDENTIFIED, THE SEARCH FOR GENETIC OR EPIGENETIC MARKERS OF FATIGUE, EITHER IN THE CONTEXT OF CF OR CHRONIC FATIGUE SYNDROME (CFS) HAS BEEN RELATIVELY UNPRODUCTIVE OR, IN THE CASE OF EPIGENETICS, NONEXISTENT. ALTHOUGH SEVERAL STUDIES, BOTH HYPOTHESIS-TESTING AND HYPOTHESIS-GENERATING, HAVE BEEN PERFORMED TO SEARCH FOR BIOMARKERS, THEY HAVE MOSTLY BEEN UNDERPOWERED, RESTRICTED BY THE HETEROGENEITY OF THE PHENOTYPE, OR LIMITED BY AN UNSYSTEMATIC STUDY DESIGN. TO BE ABLE TO CONFIRM THE HYPOTHESIS THAT RISK FOR, OR LEVELS OF, FATIGUE ARE INFLUENCED BY THE GENETIC OR EPIGENETIC BACKGROUND OF AN INDIVIDUAL, STUDIES NEED TO BE BASED ON LARGER SAMPLE SIZES WITH A MORE CLEARLY DEFINED PHENOTYPE. STUDIES NEED TO FOCUS NOT ONLY ON THE INFLUENCE OF A SINGLE ASPECT SUCH AS SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) OR DIFFERENTIAL GENE EXPRESSION ON DISEASE RISK OR STATE, BUT ALSO ON THE SYSTEMS BIOLOGY BEHIND THE DISEASE IN COMBINATION WITH INFORMATION ON ENVIRONMENTAL INFLUENCES AND VALIDATION OF FINDINGS IN FUNCTIONAL STUDIES. 2010 3 5696 27 SIMILARITIES AND DIFFERENCES IN PERIPHERAL BLOOD GENE-EXPRESSION SIGNATURES OF INDIVIDUALS WITH SCHIZOPHRENIA AND THEIR FIRST-DEGREE BIOLOGICAL RELATIVES. SEVERAL STUDIES HAVE EVALUATED THE POTENTIAL UTILITY OF BLOOD-BASED WHOLE-TRANSCRIPTOME SIGNATURES AS A SOURCE OF BIOMARKERS FOR SCHIZOPHRENIA. THIS ENDEAVOR HAS BEEN COMPLICATED BY THE FACT THAT INDIVIDUALS WITH SCHIZOPHRENIA TYPICALLY DIFFER FROM APPROPRIATE COMPARISON SUBJECTS ON MORE THAN JUST THE PRESENCE OF THE DISORDER; FOR EXAMPLE, INDIVIDUALS WITH SCHIZOPHRENIA TYPICALLY RECEIVE ANTIPSYCHOTIC MEDICATIONS, AND HAVE BEEN DEALING WITH THE SEQUELAE OF THIS CHRONIC ILLNESS FOR YEARS. THE INABILITY TO CONTROL SUCH FACTORS INTRODUCES A CONSIDERABLE DEGREE OF UNCERTAINTY IN THE RESULTS TO DATE. TO OVERCOME THIS, WE PERFORMED A BLOOD-BASED GENE-EXPRESSION PROFILING STUDY OF SCHIZOPHRENIA PATIENTS (N = 9) AS WELL AS THEIR UNMEDICATED, NONPSYCHOTIC, BIOLOGICAL SIBLINGS (N = 9) AND UNAFFECTED COMPARISON SUBJECTS (N = 12). THE UNAFFECTED BIOLOGICAL SIBLINGS, WHO MAY HARBOR SOME OF THE GENETIC PREDISPOSITION TO SCHIZOPHRENIA, EXHIBITED A HOST OF GENE-EXPRESSION DIFFERENCES FROM UNAFFECTED COMPARISON SUBJECTS, MANY OF WHICH WERE SHARED BY THEIR SCHIZOPHRENIC SIBLINGS, PERHAPS INDICATIVE OF UNDERLYING RISK FACTORS FOR THE DISORDER. SEVERAL GENES THAT WERE DYSREGULATED IN BOTH INDIVIDUALS WITH SCHIZOPHRENIA AND THEIR SIBLINGS RELATED TO NUCLEOSOME AND HISTONE STRUCTURE AND FUNCTION, SUGGESTING A POTENTIAL EPIGENETIC MECHANISM UNDERLYING THE RISK STATE FOR THE DISORDER. NONPSYCHOTIC SIBLINGS ALSO DISPLAYED SOME DIFFERENCES FROM COMPARISON SUBJECTS THAT WERE NOT FOUND IN THEIR AFFECTED SIBLINGS, SUGGESTING THAT THE DYSREGULATION OF SOME GENES IN PERIPHERAL BLOOD MAY BE INDICATIVE OF UNDERLYING PROTECTIVE FACTORS. THIS STUDY, WHILE EXPLORATORY, ILLUSTRATED THE POTENTIAL UTILITY AND INCREASED INFORMATIVENESS OF INCLUDING UNAFFECTED FIRST-DEGREE RELATIVES IN RESEARCH IN PURSUIT OF PERIPHERAL BIOMARKERS FOR SCHIZOPHRENIA. 2011 4 2901 29 GENDER DIFFERENCES IN GERM-CELL MUTAGENESIS AND GENETIC RISK. CURRENT INTERNATIONAL CLASSIFICATION SYSTEMS FOR CHEMICAL MUTAGENS ARE HAZARD-BASED RATHER THAN AIMED AT ASSESSING RISKS QUANTITATIVELY. IN THE PAST, GERM-CELL TESTS HAVE BEEN MAINLY PERFORMED WITH A LIMITED NUMBER OF SOMATIC CELL MUTAGENS, AND RARELY UNDER CONDITIONS AIMED AT COMPARING GENDER-SPECIFIC DIFFERENCES IN SUSCEPTIBILITY TO MUTAGEN EXPOSURES. THERE ARE PROFOUND DIFFERENCES IN THE GENETIC CONSTITUTION, AND IN HORMONAL, STRUCTURAL, AND FUNCTIONAL ASPECTS OF DIFFERENTIATION AND CONTROL OF GAMETOGENESIS BETWEEN THE SEXES. A CRITICAL REVIEW OF THE LITERATURE SUGGESTS THAT THESE DIFFERENCES MAY HAVE A PROFOUND IMPACT ON THE RELATIVE SUSCEPTIBILITY, STAGE OF HIGHEST SENSITIVITY AND THE RELATIVE RISK FOR THE GENESIS OF GENE MUTATION, AS WELL AS STRUCTURAL AND NUMERICAL CHROMOSOMAL ABERRATIONS IN MALE AND FEMALE GERM CELLS. TRANSMISSION OF GERM-CELL MUTATIONS TO THE OFFSPRING MAY ALSO ENCOUNTER GENDER-SPECIFIC INFLUENCES. GENDER DIFFERENCES IN SUSCEPTIBILITY TO CHEMICALLY DERIVED ALTERATIONS IN IMPRINTING PATTERNS MAY POSE A THREAT FOR THE HEALTH OF THE OFFSPRING AND MAY ALSO BE TRANSMITTED TO FUTURE GENERATIONS. RECENT REPORTS ON DIFFERENT GENETIC EFFECTS FROM HIGH ACUTE AND FROM CHRONIC LOW-DOSE EXPOSURES CHALLENGE THE VALIDITY OF CONCLUSIONS DRAWN FROM STANDARD METHODS OF MUTAGENICITY TESTING. IN CONCLUSION, RESEARCH IS URGENTLY NEEDED TO IDENTIFY GENETIC HAZARDS FOR A LARGER RANGE OF CHEMICAL COMPOUNDS, INCLUDING THOSE SUSPECTED TO DISTURB PROPER CHROMOSOME SEGREGATION. ALTERATIONS IN EPIGENETIC PROGRAMMING AND THEIR HEALTH CONSEQUENCES WILL HAVE TO BE INVESTIGATED. MORE ATTENTION SHOULD BE PAID TO GENDER-SPECIFIC GENETIC EFFECTS. FINALLY, THE DATABASE FOR GERM-CELL MUTAGENS SHOULD BE ENLARGED USING MOLECULAR METHODOLOGIES, AND GENETIC EPIDEMIOLOGY STUDIES SHOULD BE PERFORMED WITH THESE TECHNIQUES TO VERIFY HUMAN GENETIC RISK. 2007 5 5894 35 T CELL EPIGENETIC REMODELING AND ACCELERATED EPIGENETIC AGING ARE LINKED TO LONG-TERM IMMUNE ALTERATIONS IN CHILDHOOD CANCER SURVIVORS. BACKGROUND: CANCER TREATMENTS HAVE SUBSTANTIALLY IMPROVED CHILDHOOD CANCER SURVIVAL BUT ARE ACCOMPANIED BY LONG-TERM COMPLICATIONS, NOTABLY CHRONIC INFLAMMATORY DISEASES. WE HYPOTHESIZE THAT CANCER TREATMENTS COULD LEAD TO LONG-TERM EPIGENETIC CHANGES IN IMMUNE CELLS, RESULTING IN INCREASED PREVALENCE OF INFLAMMATORY DISEASES IN CANCER SURVIVORS. RESULTS: TO TEST THIS HYPOTHESIS, WE ESTABLISHED THE EPIGENETIC AND TRANSCRIPTOMIC PROFILES OF IMMUNE CELLS FROM 44 CHILDHOOD CANCER SURVIVORS (CCS, > 16 YEARS OLD) ON FULL REMISSION (> 5 YEARS) WHO HAD RECEIVED CHEMOTHERAPY ALONE OR IN COMBINATION WITH TOTAL BODY IRRADIATION (TBI) AND HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT). WE FOUND THAT MORE THAN 10 YEARS POST-TREATMENT, CCS TREATED WITH TBI/HSCT SHOWED AN ALTERED DNA METHYLATION SIGNATURE IN T CELL, PARTICULARLY AT GENES CONTROLLING IMMUNE AND INFLAMMATORY PROCESSES AND OXIDATIVE STRESS. DNA METHYLATION REMODELING IN T CELL WAS PARTIALLY ASSOCIATED WITH CHRONIC EXPRESSION CHANGES OF NEARBY GENES, INCREASED FREQUENCY OF TYPE 1 CYTOKINE-PRODUCING T CELL, ELEVATED SYSTEMIC LEVELS OF THESE CYTOKINES, AND OVER-ACTIVATION OF RELATED SIGNALING PATHWAYS. SURVIVORS EXPOSED TO TBI/HSCT WERE FURTHER CHARACTERIZED BY AN EPIGENETIC-AGING-SIGNATURE OF T CELL CONSISTENT WITH ACCELERATED EPIGENETIC AGING. TO INVESTIGATE THE POTENTIAL CONTRIBUTION OF IRRADIATION TO THESE CHANGES, WE ESTABLISHED TWO CELL CULTURE MODELS. WE IDENTIFIED THAT RADIATION PARTIALLY RECAPITULATED THE IMMUNE CHANGES OBSERVED IN SURVIVORS THROUGH A BYSTANDER EFFECT THAT COULD BE MEDIATED BY CIRCULATING FACTORS. CONCLUSION: CANCER TREATMENTS, IN PARTICULAR TBI/HSCT, ARE ASSOCIATED WITH LONG-TERM IMMUNE DISTURBANCES. WE PROPOSE THAT EPIGENETIC REMODELING OF IMMUNE CELLS FOLLOWING CANCER THERAPY AUGMENTS INFLAMMATORY- AND AGE-RELATED DISEASES, INCLUDING METABOLIC COMPLICATIONS, IN CHILDHOOD CANCER SURVIVORS. 2018 6 6697 36 VARICELLA-ZOSTER VIRUS HUMAN GANGLIONIC LATENCY: A CURRENT SUMMARY. VARICELLA-ZOSTER VIRUS (VZV) IS A UBIQUITOUS HUMAN HERPES VIRUS TYPICALLY ACQUIRED IN CHILDHOOD WHEN IT CAUSES VARICELLA (CHICKENPOX), FOLLOWING WHICH THE VIRUS ESTABLISHES A LATENT INFECTION IN TRIGEMINAL AND DORSAL ROOT GANGLIA THAT LASTS FOR THE LIFE OF THE INDIVIDUAL. VZV SUBSEQUENTLY REACTIVATES, SPONTANEOUSLY OR AFTER SPECIFIC TRIGGERING FACTORS, TO CAUSE HERPES ZOSTER (SHINGLES), WHICH MAY BE COMPLICATED BY POSTHERPETIC NEURALGIA AND SEVERAL OTHER NEUROLOGICAL COMPLICATIONS INCLUDING VASCULOPATHY. OUR UNDERSTANDING OF VZV LATENCY LAGS BEHIND OUR KNOWLEDGE OF HERPES SIMPLEX VIRUS TYPE 1 (HSV-1) LATENCY PRIMARILY DUE TO THE DIFFICULTY IN PROPAGATING THE VIRUS TO HIGH TITERS IN A CELL-FREE STATE, AND THE LACK OF A SUITABLE SMALL-ANIMAL MODEL FOR STUDYING VIRUS LATENCY AND REACTIVATION. IT IS NOW ESTABLISHED BEYOND DOUBT THAT LATENT VZV IS PREDOMINANTLY LOCATED IN HUMAN GANGLIONIC NEURONS. VIRUS GENE TRANSCRIPTION DURING LATENCY IS EPIGENETICALLY REGULATED, AND APPEARS TO BE RESTRICTED TO EXPRESSION OF AT LEAST SIX GENES, WITH EXPRESSION OF GENE 63 BEING THE HALLMARK OF LATENCY. HOWEVER, VIRAL GENE TRANSCRIPTION MAY BE MORE EXTENSIVE THAN PREVIOUSLY THOUGHT. THERE IS ALSO EVIDENCE FOR SEVERAL VZV GENES BEING EXPRESSED AT THE PROTEIN LEVEL, INCLUDING VZV GENE 63-ENCODED PROTEIN, BUT RECENT EVIDENCE SUGGESTS THAT THIS MAY NOT BE A COMMON EVENT. THE NATURE AND EXTENT OF THE CHRONIC INFLAMMATORY RESPONSE IN LATENTLY INFECTED GANGLIA IS ALSO OF CURRENT INTEREST. THERE REMAIN SEVERAL QUESTIONS CONCERNING THE VZV LATENCY PROCESS THAT STILL NEED TO BE RESOLVED UNAMBIGUOUSLY AND IT IS LIKELY THAT THIS WILL REQUIRE THE USE OF NEWLY DEVELOPED MOLECULAR TECHNOLOGIES, SUCH AS GEXPS MULTIPLEX POLYMERASE CHAIN REACTION (PCR) FOR VIRUS TRANSCRIPTIONAL ANALYSIS AND CHIP-SEQ TO STUDY THE EPIGENETIC OF LATENT VIRUS GENOME ( LIU ET AL, 2010 , BMC BIOL 8: 56). 2010 7 5649 21 SEX DIFFERENCES IN PSYCHOSTIMULANT ABUSE: IMPLICATIONS FOR ESTROGEN RECEPTORS AND HISTONE DEACETYLASES. SUBSTANCE ABUSE IS A CHRONIC PATHOLOGICAL DISORDER THAT NEGATIVELY AFFECTS MANY HEALTH AND NEUROLOGICAL PROCESSES. A GROWING BODY OF LITERATURE HAS REVEALED GENDER DIFFERENCES IN SUBSTANCE USE. COMPARED TO MEN, WOMEN DISPLAY DISTINCT DRUG-USE PHENOTYPES ACCOMPANIED BY RECOVERY AND REHABILITATION DISPARITIES. THESE OBSERVATIONS HAVE LED TO THE NOTION THAT SEX-DEPENDENT SUSCEPTIBILITIES EXIST ALONG THE PROGRESSION TO ADDICTION. WITHIN THIS SCOPE, NEUROADAPTATIONS FOLLOWING PSYCHOSTIMULANT EXPOSURE ARE THOUGHT TO BE DISTINCT FOR EACH SEX. THIS REVIEW SUMMARIZES CLINICAL FINDINGS AND ANIMAL RESEARCH REPORTING SEX DIFFERENCES IN THE SUBJECTIVE AND BEHAVIORAL RESPONSES TO COCAINE, METHAMPHETAMINE, AND NICOTINE. THIS DISCUSSION IS FOLLOWED BY AN EXAMINATION OF EPIGENETIC AND MOLECULAR ALTERATIONS IMPLICATED IN THE ADDICTION PROCESS. SPECIAL CONSIDERATION IS GIVEN TO HISTONE DEACETYLASES AND ESTROGEN RECEPTOR-MEDIATED GENE EXPRESSION. 2022 8 1314 26 DELINEATING CONDITIONS AND SUBTYPES IN CHRONIC PAIN USING NEUROIMAGING. DIFFERENTIATING SUBTYPES OF CHRONIC PAIN STILL REMAINS A CHALLENGE-BOTH FROM A SUBJECTIVE AND OBJECTIVE POINT OF VIEW. PERSONALIZED MEDICINE IS THE CURRENT GOAL OF MODERN MEDICAL CARE AND IS LIMITED BY THE SUBJECTIVE NATURE OF PATIENT SELF-REPORTING OF SYMPTOMS AND BEHAVIORAL EVALUATION. PHYSIOLOGY-FOCUSED TECHNIQUES SUCH AS GENOME AND EPIGENETIC ANALYSES INFORM THE DELINEATION OF PAIN GROUPS; HOWEVER, EXCEPT UNDER RARE CIRCUMSTANCES, THEY HAVE DILUTED EFFECTS THAT AGAIN, SHARE A COMMON RELIANCE ON BEHAVIORAL EVALUATION. THE APPLICATION OF STRUCTURAL NEUROIMAGING TOWARDS DISTINGUISHING PAIN SUBTYPES IS A GROWING FIELD AND MAY INFORM PAIN-GROUP CLASSIFICATION THROUGH THE ANALYSIS OF BRAIN REGIONS SHOWING HYPERTROPHIC AND ATROPHIC CHANGES IN THE PRESENCE OF PAIN. ANALYTICAL TECHNIQUES SUCH AS MACHINE-LEARNING CLASSIFIERS HAVE THE CAPACITY TO PROCESS LARGE VOLUMES OF DATA AND DELINEATE DIAGNOSTICALLY RELEVANT INFORMATION FROM NEUROIMAGING ANALYSIS. THE ISSUE OF DEFINING A "BRAIN TYPE" IS AN EMERGING FIELD AIMED AT INTERPRETING OBSERVED BRAIN CHANGES AND DELINEATING THEIR CLINICAL IDENTITY/SIGNIFICANCE. IN THIS REVIEW, 2 CHRONIC PAIN CONDITIONS (MIGRAINE AND IRRITABLE BOWEL SYNDROME) WITH SIMILAR CLINICAL PHENOTYPES ARE COMPARED IN TERMS OF THEIR STRUCTURAL NEUROIMAGING FINDINGS. INDEPENDENT INVESTIGATIONS ARE COMPARED WITH FINDINGS FROM APPLICATION OF MACHINE-LEARNING ALGORITHMS. FINDINGS ARE DISCUSSED IN TERMS OF DIFFERENTIATING PATIENT SUBGROUPS USING NEUROIMAGING DATA IN PATIENTS WITH CHRONIC PAIN AND HOW THEY MAY BE APPLIED TOWARDS DEFINING A PERSONALIZED PAIN SIGNATURE THAT HELPS SEGREGATE PATIENT SUBGROUPS (EG, MIGRAINE WITH AND WITHOUT AURA, WITH OR WITHOUT NAUSEA; IRRITABLE BOWEL SYNDROME VS OTHER FUNCTIONAL GASTROINTESTINAL DISORDERS). 2019 9 6323 30 THE ROLE OF A POTENTIAL BIOMARKER IN PATIENTS WITH MIGRAINE: REVIEW AND NEW INSIGHTS. INTRODUCTION: THE SEARCH FOR AN IDEAL BIOMARKER FOR MIGRAINE HAS PERSISTED FOR A LONG TIME. THERE IS PLENTIFUL EVIDENCE OF POTENTIAL BIOMARKERS FOR MIGRAINE FOUND IN CEREBROSPINAL FLUID, BLOOD, AND SALIVA.AREAS COVERED: HEREIN, THE AUTHORS HIGHLIGHT AND DISCUSS THE MOST PROMISING CANDIDATES IN THE LITERATURE. AN ELECTRONIC SEARCH WAS PERFORMED FOR STUDIES PUBLISHED BETWEEN 2010 AND 2020 IN MEDLINE, PUBMED, AND EMBASE, RELATED TO POTENTIAL BIOMARKERS IN MIGRAINE PATIENTS, FOUND IN CEREBROSPINAL FLUID, SALIVA, AND SERUM, FOCUSING ON BIOMARKERS THAT CAN BE RELATED TO TREATMENT AND CLINICAL OUTCOMES.EXPERT OPINION: AN IDEAL BIOMARKER, OR A PANEL OF BIOMARKERS, COULD REVOLUTIONIZE THE WAY WE ADDRESS AND PROPOSE TREATMENTS FOR THIS DISEASE. ONCE SEVERE PRESENTATIONS AND PHENOTYPES HAVE BEEN IDENTIFIED USING A RELIABLE BIOMARKER, PATIENTS COULD BE TREATED AT EARLIER DISEASE STAGES WITH MORE SPECIFIC MEDICATIONS. THE MOST IMPORTANT BIOMARKERS WITH THE MOST SIGNIFICANT LEVELS OF EVIDENCE COMPRISED CALCITONIN GENE-RELATED PEPTIDE (CGRP), GLUTAMATE, NERVE GROWTH FACTOR, SOME INFLAMMATORY (CRP, TNF-ALPHA, INTERLEUKINS) AND OXIDATIVE STRESS MARKERS. CGRP WAS ASSOCIATED WITH EPISODIC, CHRONIC MIGRAINE AND RESPONSE TO TREATMENT. PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE IS AN EMERGING NEUROPEPTIDE INVOLVED IN MIGRAINE DIAGNOSTICS AND SEVERITY. NEW GENETIC AND EPIGENETIC BIOMARKERS WILL BE CANDIDATES FOR FUTURE RESEARCH. 2021 10 247 31 ADULTHOOD ASTHMA AS A CONSEQUENCE OF CHILDHOOD ADVERSITY: A SYSTEMATIC REVIEW OF EPIGENETICALLY AFFECTED GENES. THERE IS AN ACCUMULATING DATA THAT SHOWS RELATION BETWEEN CHILDHOOD ADVERSITY AND VULNERABILITY TO CHRONIC DISEASES AS WELL AS EPIGENETIC INFLUENCES THAT IN TURN GIVE RISE TO THESE DISEASES. ASTHMA IS ONE OF THE CHRONIC DISEASES THAT IS INFLUENCED FROM GENETIC REGULATION OF THE INFLAMMATORY BIOMOLECULES AND THEREFORE THE HYPOTHESIS IN THIS RESEARCH WAS CHILDHOOD ADVERSITY MIGHT HAVE CAUSED EPIGENETIC DIFFERENTIATION IN THE ASTHMA-RELATED GENES IN THE POPULATION WHO HAD CHILDHOOD TRAUMA. TO TEST THIS HYPOTHESIS, THE LITERATURE WAS SYSTEMATICALLY REVIEWED TO EXTRACT EPIGENETICALLY MODIFIED GENE DATA OF THE ADULTS WHO HAD CHILDHOOD ADVERSITY, AND AFFECTED GENES WERE FURTHER EVALUATED FOR THEIR ASSOCIATION WITH ASTHMA. PRISMA GUIDELINES WERE ADOPTED AND PUBMED AND GOOGLE SCHOLAR WERE INCLUDED IN THE SEARCHED DATABASES, TO EVALUATE EPIGENETIC MODIFICATIONS IN ASTHMA-RELATED GENES OF PHYSICALLY, EMOTIONALLY OR SEXUALLY ABUSED CHILDREN. AFTER RETRIEVING A TOTAL OF 5245 ARTICLES, 36 OF THEM WERE INCLUDED IN THE STUDY. SEVERAL GENES AND PATHWAYS THAT MAY CONTRIBUTE TO PATHOGENESIS OF ASTHMA DEVELOPMENT, INCREASED INFLAMMATION, OR RESPONSE TO ASTHMA TREATMENT WERE FOUND EPIGENETICALLY AFFECTED BY CHILDHOOD TRAUMAS. CHILDHOOD ADVERSITY, CAUSING EPIGENETIC CHANGES IN DNA, MAY LEAD TO ASTHMA DEVELOPMENT OR INFLUENCE THE COURSE OF THE DISEASE AND THEREFORE SHOULD BE TAKEN INTO ACCOUNT FOR THE PROLONGED HEALTH CONSEQUENCES. 2022 11 2571 25 EPIGENETICS OF CHRONIC PAIN AFTER THORACIC SURGERY. PURPOSE OF REVIEW: CHRONIC PAIN AFTER SURGERY IS A MAJOR PUBLIC HEALTH PROBLEM AND A MAJOR CONCERN FOR PERIOPERATIVE PHYSICIANS. THORACIC SURGERY PRESENTS A UNIQUE CHALLENGE, AS THORACOTOMY IS AMONG THE HIGHEST RISK SURGERIES TO DEVELOP PERSISTENT POSTSURGICAL PAIN. THE PURPOSE OF THIS REVIEW IS TO DISCUSS THE RELEVANCE OF RESEARCH IN PAIN EPIGENETICS TO PATIENTS WITH PERSISTENT PAIN AFTER THORACIC SURGERY. RECENT FINDINGS: RECENT ADVANCES HAVE LINKED CHRONIC PAIN STATES TO GENETIC AND EPIGENETIC CHANGES. PROGRESS IN OUR UNDERSTANDING OF CHRONIC PAIN HAS HIGHLIGHTED THE IMPORTANCE OF IMMUNE MODULATION OF PAIN. IT IS POSSIBLE THAT EPIGENETIC CHANGES DRIVING CHRONIC PAIN OCCUR IN THE PERIOPERATIVE SETTING VIA HISTONE MODIFICATION AND DNA METHYLATION. SUMMARY: THE TRANSITION FROM ACUTE TO CHRONIC PAIN AFTER THORACIC SURGERY MAY BE MEDIATED BY EPIGENETICS. HERE, WE DISCUSS EPIGENETIC MODIFICATIONS THAT HAVE BEEN DISCOVERED IN ANIMAL MODELS OF CHRONIC PAIN THAT MAY PREDISPOSE PATIENTS TO PERSISTENT NEUROPATHIC PAIN AFTER THORACIC SURGERY. 2014 12 2816 35 FIBROMYALGIA: PATHOGENESIS, MECHANISMS, DIAGNOSIS AND TREATMENT OPTIONS UPDATE. FIBROMYALGIA IS A SYNDROME CHARACTERIZED BY CHRONIC AND WIDESPREAD MUSCULOSKELETAL PAIN, OFTEN ACCOMPANIED BY OTHER SYMPTOMS, SUCH AS FATIGUE, INTESTINAL DISORDERS AND ALTERATIONS IN SLEEP AND MOOD. IT IS ESTIMATED THAT TWO TO EIGHT PERCENT OF THE WORLD POPULATION IS AFFECTED BY FIBROMYALGIA. FROM A MEDICAL POINT OF VIEW, THIS PATHOLOGY STILL PRESENTS INEXPLICABLE ASPECTS. IT IS KNOWN THAT FIBROMYALGIA IS CAUSED BY A CENTRAL SENSITIZATION PHENOMENON CHARACTERIZED BY THE DYSFUNCTION OF NEURO-CIRCUITS, WHICH INVOLVES THE PERCEPTION, TRANSMISSION AND PROCESSING OF AFFERENT NOCICEPTIVE STIMULI, WITH THE PREVALENT MANIFESTATION OF PAIN AT THE LEVEL OF THE LOCOMOTOR SYSTEM. IN RECENT YEARS, THE PATHOGENESIS OF FIBROMYALGIA HAS ALSO BEEN LINKED TO OTHER FACTORS, SUCH AS INFLAMMATORY, IMMUNE, ENDOCRINE, GENETIC AND PSYCHOSOCIAL FACTORS. A RHEUMATOLOGIST TYPICALLY MAKES A DIAGNOSIS OF FIBROMYALGIA WHEN THE PATIENT DESCRIBES A HISTORY OF PAIN SPREADING IN ALL QUADRANTS OF THE BODY FOR AT LEAST THREE MONTHS AND WHEN PAIN IS CAUSED BY DIGITAL PRESSURE IN AT LEAST 11 OUT OF 18 ALLOGENIC POINTS, CALLED TENDER POINTS. FIBROMYALGIA DOES NOT INVOLVE ORGANIC DAMAGE, AND SEVERAL DIAGNOSTIC APPROACHES HAVE BEEN DEVELOPED IN RECENT YEARS, INCLUDING THE ANALYSIS OF GENETIC, EPIGENETIC AND SEROLOGICAL BIOMARKERS. SYMPTOMS OFTEN BEGIN AFTER PHYSICAL OR EMOTIONAL TRAUMA, BUT IN MANY CASES, THERE APPEARS TO BE NO OBVIOUS TRIGGER. WOMEN ARE MORE PRONE TO DEVELOPING THE DISEASE THAN MEN. UNFORTUNATELY, THE CONVENTIONAL MEDICAL THERAPIES THAT TARGET THIS PATHOLOGY PRODUCE LIMITED BENEFITS. THEY REMAIN LARGELY PHARMACOLOGICAL IN NATURE AND TEND TO TREAT THE SYMPTOMATIC ASPECTS OF VARIOUS DISORDERS REPORTED BY THE PATIENT. THE STATISTICS, HOWEVER, HIGHLIGHT THE FACT THAT 90% OF PEOPLE WITH FIBROMYALGIA ALSO TURN TO COMPLEMENTARY MEDICINE TO MANAGE THEIR SYMPTOMS. 2021 13 1045 30 CLINICAL CORRELATION AMONG MALE INFERTILITY AND OVERALL MALE HEALTH: A SYSTEMATIC REVIEW OF THE LITERATURE. PURPOSE: ONGOING EVIDENCE HAS SUGGESTED THE ROLE OF MALE FACTOR INFERTILITY AS A POTENTIAL PREDICTOR OF MORTALITY AND GENERAL HEALTH STATUS. THE AIM OF THE PRESENT REVIEW IS TO UPDATE THE CURRENT KNOWLEDGE BASE REGARDING THE ASSOCIATION BETWEEN MALE FACTOR INFERTILITY AND GENERAL HEALTH THROUGH A CRITICAL REVIEW OF THE LITERATURE. MATERIALS AND METHODS: A SYSTEMATIC REVIEW OF THE LITERATURE WAS CARRIED OUT FROM INCEPTION TO NOVEMBER 2019 IN ORDER TO EVALUATE SIGNIFICANT ASSOCIATIONS BETWEEN MALE INFERTILITY AND ADVERSE HEALTH OUTCOMES SUCH AS CARDIOVASCULAR, ONCOLOGIC, METABOLIC AND AUTOIMMUNE DISEASES AS WELL AS OVERALL MORTALITY. RESULTS: IN ALL, 27 STUDIES MET INCLUSION CRITERIA AND WERE CRITICALLY EXAMINED. FIVE STUDIES EXAMINED MALE INFERTILITY AND CARDIOVASCULAR DISEASE RISK, 11 EXAMINED ONCOLOGIC RISK (E.G., OVERALL CANCER RISK, TESTIS AND PROSTATE CANCER), 8 EXAMINED AGGREGATE CHRONIC MEDICAL DISEASES AND 5 INFERTILITY RELATED TO INCIDENCE OF MORTALITY, FOR A TOTAL OF 599,807 MEN DIAGNOSED WITH ANY MALE FACTOR INFERTILITY COVERING A PERIOD FROM 1916 TO 2016. CONCLUSIONS: A MAN'S FERTILITY AND OVERALL HEALTH APPEAR TO BE INTERCONNECTED. THEREFORE, A DIAGNOSIS OF MALE INFERTILITY MAY ALLOW A WINDOW INTO FUTURE COMORBIDITY AND/OR MORTALITY WHICH MAY HELP GUIDE CLINICAL DECISIONS AND COUNSELING. SEVERAL POSSIBLE ETIOLOGIES SUCH AS GENETIC, EPIGENETIC, DEVELOPMENTAL, AND LIFESTYLE-BASED FACTORS NEED TO BE FURTHER EVALUATED IN ORDER TO ESTABLISH THE UNDERLYING MECHANISMS BETWEEN MALE INFERTILITY AND HEALTH. 2020 14 40 39 A COMPARISON OF HERPES SIMPLEX VIRUS TYPE 1 AND VARICELLA-ZOSTER VIRUS LATENCY AND REACTIVATION. HERPES SIMPLEX VIRUS TYPE 1 (HSV-1; HUMAN HERPESVIRUS 1) AND VARICELLA-ZOSTER VIRUS (VZV; HUMAN HERPESVIRUS 3) ARE HUMAN NEUROTROPIC ALPHAHERPESVIRUSES THAT CAUSE LIFELONG INFECTIONS IN GANGLIA. FOLLOWING PRIMARY INFECTION AND ESTABLISHMENT OF LATENCY, HSV-1 REACTIVATION TYPICALLY RESULTS IN HERPES LABIALIS (COLD SORES), BUT CAN OCCUR FREQUENTLY ELSEWHERE ON THE BODY AT THE SITE OF PRIMARY INFECTION (E.G. WHITLOW), PARTICULARLY AT THE GENITALS. RARELY, HSV-1 REACTIVATION CAN CAUSE ENCEPHALITIS; HOWEVER, A THIRD OF THE CASES OF HSV-1 ENCEPHALITIS ARE ASSOCIATED WITH HSV-1 PRIMARY INFECTION. PRIMARY VZV INFECTION CAUSES VARICELLA (CHICKENPOX) FOLLOWING WHICH LATENT VIRUS MAY REACTIVATE DECADES LATER TO PRODUCE HERPES ZOSTER (SHINGLES), AS WELL AS AN INCREASINGLY RECOGNIZED NUMBER OF SUBACUTE, ACUTE AND CHRONIC NEUROLOGICAL CONDITIONS. FOLLOWING PRIMARY INFECTION, BOTH VIRUSES ESTABLISH A LATENT INFECTION IN NEURONAL CELLS IN HUMAN PERIPHERAL GANGLIA. HOWEVER, THE DETAILED MECHANISMS OF VIRAL LATENCY AND REACTIVATION HAVE YET TO BE UNRAVELLED. IN BOTH CASES LATENT VIRAL DNA EXISTS IN AN 'END-LESS' STATE WHERE THE ENDS OF THE VIRUS GENOME ARE JOINED TO FORM STRUCTURES CONSISTENT WITH UNIT LENGTH EPISOMES AND CONCATEMERS, FROM WHICH VIRAL GENE TRANSCRIPTION IS RESTRICTED. IN LATENTLY INFECTED GANGLIA, THE MOST ABUNDANTLY DETECTED HSV-1 RNAS ARE THE SPLICED PRODUCTS ORIGINATING FROM THE PRIMARY LATENCY ASSOCIATED TRANSCRIPT (LAT). THIS PRIMARY LAT IS AN 8.3 KB UNSTABLE TRANSCRIPT FROM WHICH TWO STABLE (1.5 AND 2.0 KB) INTRONS ARE SPLICED. TRANSCRIPTS MAPPING TO 12 VZV GENES HAVE BEEN DETECTED IN HUMAN GANGLIA REMOVED AT AUTOPSY; HOWEVER, IT IS DIFFICULT TO ASCRIBE THESE AS TRANSCRIPTS PRESENT DURING LATENT INFECTION AS EARLY-STAGE VIRUS REACTIVATION MAY HAVE TRANSPIRED IN THE POST-MORTEM TIME PERIOD IN THE GANGLIA. NONETHELESS, LOW-LEVEL TRANSCRIPTION OF VZV ORF63 HAS BEEN REPEATEDLY DETECTED IN MULTIPLE GANGLIA REMOVED AS CLOSE TO DEATH AS POSSIBLE. THERE IS INCREASING EVIDENCE THAT HSV-1 AND VZV LATENCY IS EPIGENETICALLY REGULATED. IN VITRO MODELS THAT PERMIT PATHWAY ANALYSIS AND IDENTIFICATION OF BOTH EPIGENETIC MODULATIONS AND GLOBAL TRANSCRIPTIONAL MECHANISMS OF HSV-1 AND VZV LATENCY HOLD MUCH PROMISE FOR OUR FUTURE UNDERSTANDING IN THIS COMPLEX AREA. THIS REVIEW SUMMARIZES THE MOLECULAR BIOLOGY OF HSV-1 AND VZV LATENCY AND REACTIVATION, AND ALSO PRESENTS FUTURE DIRECTIONS FOR STUDY. 2015 15 1599 27 DNA METHYLATION SIGNATURE OF CHILDHOOD CHRONIC PHYSICAL AGGRESSION IN T CELLS OF BOTH MEN AND WOMEN. BACKGROUND: HIGH FREQUENCY OF PHYSICAL AGGRESSION IS THE CENTRAL FEATURE OF SEVERE CONDUCT DISORDER AND IS ASSOCIATED WITH A WIDE RANGE OF SOCIAL, MENTAL AND PHYSICAL HEALTH PROBLEMS. WE HAVE PREVIOUSLY TESTED THE HYPOTHESIS THAT DIFFERENTIAL DNA METHYLATION SIGNATURES IN PERIPHERAL T CELLS ARE ASSOCIATED WITH A CHRONIC AGGRESSION TRAJECTORY IN MALES. DESPITE THE FACT THAT SEX DIFFERENCES APPEAR TO PLAY A PIVOTAL ROLE IN DETERMINING THE DEVELOPMENT, MAGNITUDE AND FREQUENCY OF AGGRESSION, MOST OF PREVIOUS STUDIES FOCUSED ON MALES, SO LITTLE IS KNOWN ABOUT FEMALE CHRONIC PHYSICAL AGGRESSION. WE THEREFORE TESTED HERE WHETHER OR NOT THERE IS A SIGNATURE OF PHYSICAL AGGRESSION IN FEMALE DNA METHYLATION AND, IF THERE IS, HOW IT RELATES TO THE SIGNATURE OBSERVED IN MALES. METHODOLOGY/PRINCIPAL FINDINGS: METHYLATION PROFILES WERE CREATED USING THE METHOD OF METHYLATED DNA IMMUNOPRECIPITATION (MEDIP) FOLLOWED BY MICROARRAY HYBRIDIZATION AND STATISTICAL AND BIOINFORMATIC ANALYSES ON T CELL DNA OBTAINED FROM ADULT WOMEN WHO WERE FOUND TO BE ON A CHRONIC PHYSICAL AGGRESSION TRAJECTORY (CPA) BETWEEN 6 AND 12 YEARS OF AGE COMPARED TO WOMEN WHO FOLLOWED A NORMAL PHYSICAL AGGRESSION TRAJECTORY. WE CONFIRMED THE EXISTENCE OF A WELL-DEFINED, GENOME-WIDE SIGNATURE OF DNA METHYLATION ASSOCIATED WITH CHRONIC PHYSICAL AGGRESSION IN THE PERIPHERAL T CELLS OF ADULT FEMALES THAT INCLUDES MANY OF THE GENES SIMILARLY ASSOCIATED WITH PHYSICAL AGGRESSION IN THE SAME CELL TYPES OF ADULT MALES. CONCLUSIONS: THIS STUDY IN A SMALL NUMBER OF WOMEN PRESENTS PRELIMINARY EVIDENCE FOR A GENOME-WIDE VARIATION IN PROMOTER DNA METHYLATION THAT ASSOCIATES WITH CPA IN WOMEN THAT WARRANT LARGER STUDIES FOR FURTHER VERIFICATION. A SIGNIFICANT PROPORTION OF THESE ASSOCIATIONS WERE PREVIOUSLY OBSERVED IN MEN WITH CPA SUPPORTING THE HYPOTHESIS THAT THE EPIGENETIC SIGNATURE OF EARLY LIFE AGGRESSION IN FEMALES IS COMPOSED OF A COMPONENT SPECIFIC TO FEMALES AND ANOTHER COMMON TO BOTH MALES AND FEMALES. 2014 16 1844 32 EFFECTS OF THE LIFESTYLE HABITS IN BREAST CANCER TRANSCRIPTIONAL REGULATION. THROUGH RESEARCH CARRIED OUT IN THE LAST 25 YEARS ABOUT THE BREAST CANCER ETIOLOGY, IT HAS BEEN POSSIBLE TO ESTIMATE THAT LESS THAN 10 % OF PATIENTS WHO ARE DIAGNOSED WITH THE CONDITION ARE CARRIERS OF SOME GERMLINE OR SOMATIC MUTATION. THE CLINICAL REPORTS OF BREAST CANCER PATIENTS WITH HEALTHY TWINS AND THE DEVELOPMENT OF DISEASE IN WOMEN WITHOUT HIGH PENETRANCE MUTATIONS DETECTED, WARN THE PARTICIPATION MORE FACTORS IN THE TRANSFORMATION PROCESS. THE HIGH INCIDENCE OF MAMMARY ADENOCARCINOMA IN THE MODERN WOMAN AND THE URGENT NEED FOR NEW METHODS OF PREVENTION AND EARLY DETECTION HAVE DEMANDED MORE INFORMATION ABOUT THE ROLE THAT ENVIRONMENT AND LIFESTYLE HAVE ON THE TRANSFORMATION OF MAMMARY GLAND EPITHELIAL CELLS. OBESITY, ALCOHOLISM AND SMOKING ARE FACTORS THAT HAVE SHOWN A CLOSE CORRELATION WITH THE RISK OF DEVELOPING BREAST CANCER. AND ALTHOUGH THESE CONDITIONS AFFECT DIFFERENT CELL REGULATION LEVELS, THE STUDY OF ITS EFFECTS IN THE MECHANISMS OF TRANSCRIPTIONAL AND EPIGENETIC REGULATION IS CONSIDERED CRITICAL FOR A BETTER UNDERSTANDING OF THE LOSS OF IDENTITY OF EPITHELIAL CELLS DURING CARCINOGENESIS OF THIS TISSUE. THE MAIN OBJECTIVE OF THIS REVIEW WAS TO ESTABLISH THE IMPORTANCE OF CHANGES OCCURRING TO TRANSCRIPTIONAL LEVEL IN THE MAMMARY GLAND AS A CONSEQUENCE OF ACUTE OR CHRONIC EXPOSURE TO HARMFUL PRODUCTS SUCH AS OBESITY-CAUSING FOODS, ETHANOL AND CIGARETTE SMOKE COMPONENTS. AT ANALYZE THE MAIN STUDIES RELATED TO TOPIC, IT HAS CONCLUDED THAT THE UNDERSTANDING OF EFFECTS CAUSED BY THE LIFESTYLE FACTORS IN PERFORMANCE OF THE TRANSCRIPTIONAL MECHANISMS THAT DETERMINE GENE EXPRESSION OF THE MAMMARY GLAND EPITHELIAL CELLS, MAY HELP EXPLAIN THE DEVELOPMENT OF THIS DISEASE IN WOMEN WITHOUT GENETIC PROPENSITY AND DIFFERENT PHENOTYPIC MANIFESTATIONS OF THIS CANCER TYPE. 2016 17 2108 30 EPIGENETIC FACTORS RELATED TO LOW BACK PAIN: A SYSTEMATIC REVIEW OF THE CURRENT LITERATURE. LOW BACK PAIN (LBP) IS ONE OF THE MOST COMMON CAUSES OF PAIN AND DISABILITY. AT PRESENT, TREATMENT AND INTERVENTIONS FOR ACUTE AND CHRONIC LOW BACK PAIN OFTEN FAIL TO PROVIDE SUFFICIENT LEVELS OF PAIN RELIEF, AND FULL FUNCTIONAL RESTORATION CAN BE CHALLENGING. CONSIDERING THE SIGNIFICANT SOCIO-ECONOMIC BURDEN AND RISK-TO-BENEFIT RATIO OF MEDICAL AND SURGICAL INTERVENTION IN LOW BACK PAIN PATIENTS, THE IDENTIFICATION OF RELIABLE BIOMARKERS SUCH AS EPIGENETIC FACTORS ASSOCIATED WITH LOW BACK PAIN COULD BE USEFUL IN CLINICAL PRACTICE. THE AIM OF THIS STUDY WAS TO REVIEW THE AVAILABLE LITERATURE REGARDING THE EPIGENETIC FACTORS ASSOCIATED WITH LOW BACK PAIN. THIS REVIEW WAS CARRIED OUT IN ACCORDANCE WITH PREFERENTIAL REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES (PRISMA) GUIDELINES. THE SEARCH WAS CARRIED OUT IN OCTOBER 2022. ONLY PEER-REVIEWED ARTICLES WERE CONSIDERED FOR INCLUSION. FOURTEEN STUDIES WERE INCLUDED AND SHOWED PROMISING RESULTS IN TERMS OF RELIABLE MARKERS. EPIGENETIC MARKERS FOR LBP HAVE THE POTENTIAL TO SIGNIFICANTLY MODIFY DISEASE MANAGEMENT. MOST RECENT EVIDENCE SUGGESTS THAT EPIGENETICS IS A MORE PROMISING FIELD FOR THE IDENTIFICATION OF FACTORS ASSOCIATED WITH LBP, OFFERING A RATIONALE FOR FURTHER INVESTIGATION IN THIS FIELD WITH THE LONG-TERM GOAL OF FINDING EPIGENETIC BIOMARKERS THAT COULD CONSTITUTE BIOLOGICAL TARGETS FOR DISEASE MANAGEMENT AND TREATMENT. 2023 18 2093 28 EPIGENETIC EFFECTS FOLLOWING ACUTE AND CHRONIC EXERCISE IN CARDIOVASCULAR DISEASE: A SYSTEMATIC REVIEW. INTRODUCTION: ACUTE EXERCISE AND EXERCISE TRAINING MAY CONFER EPIGENETIC MODIFICATIONS IN HEALTHY SUBJECTS. EPIGENETIC EFFECTS AFTER EXERCISE HAVE BEEN SHOWED IN PATIENTS WITH CARDIOVASCULAR DISEASE. THE AIM OF THIS SYSTEMATIC REVIEW WAS TO SUMMARIZE THE EVIDENCE FROM AVAILABLE CLINICAL TRIALS THAT STUDY EPIGENETIC ADAPTATIONS AFTER EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. METHODS: THE SEARCH STRATEGY WAS PERFORMED IN PUBMED AND CENTRAL DATABASES ON ARTICLES PUBLISHED UNTIL SEPTEMBER 2020. STUDIES WITH TITLES AND ABSTRACTS RELEVANT TO EXERCISE EPIGENETIC MODIFICATION APPLIED TO CARDIOVASCULAR PATIENTS WERE FULLY EXAMINED. INCLUSION AND EXCLUSION CRITERIA WERE UTILIZED FOR STUDIES SCREENING. QUALITY ASSESSMENT WITH PEDRO SCALE AND EVALUATION BY TWO INDEPENDENT REVIEWERS WAS PERFORMED. RESULTS: OF THE 1714 ARTICLES RETRIEVED, 88 ARTICLES WERE ASSESSED FOR ELIGIBILITY CRITERIA AND 8 ARTICLES MATCHED OUR SEARCH CRITERIA AND FINALLY INCLUDED IN THE SYSTEMATIC ANALYSIS. THE ACUTE EXERCISE EPIGENETIC (MIRNAS) EFFECTS WERE ASSESSED IN THREE STUDIES AND THE CHRONIC EXERCISE TRAINING EFFECTS (MIRNAS AND DNA METHYLATION) IN SIX STUDIES. THE RESULTS HAVE SHOWN THAT THERE IS POSSIBLY AN ACUTE SIGNIFICANT EXERCISE EFFECT ON EPIGENETIC TARGETS WHICH IS MORE EVIDENT AFTER CHRONIC EXERCISE TRAINING. CONCLUSIONS: BY THE PRESENT SYSTEMATIC REVIEW, WE PROVIDE PRELIMINARY EVIDENCE OF BENEFICIAL EPIGENETIC ADAPTATIONS FOLLOWING ACUTE AND CHRONIC EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. MORE CONTROLLED STUDIES ARE NEEDED TO CONFIRM SUCH EVIDENCE. 2021 19 2507 26 EPIGENETICS AND OBESITY: THE DEVIL IS IN THE DETAILS. OBESITY IS A COMPLEX DISEASE WITH MULTIPLE WELL-DEFINED RISK FACTORS. NEVERTHELESS, SUSCEPTIBILITY TO OBESITY AND ITS SEQUELAE WITHIN OBESOGENIC ENVIRONMENTS VARIES GREATLY FROM ONE PERSON TO THE NEXT, SUGGESTING A ROLE FOR GENE X ENVIRONMENT INTERACTIONS IN THE ETIOLOGY OF THE DISORDER. EPIGENETIC REGULATION OF THE HUMAN GENOME PROVIDES A PUTATIVE MECHANISM BY WHICH SPECIFIC ENVIRONMENTAL EXPOSURES CONVEY RISK FOR OBESITY AND OTHER HUMAN DISEASES AND IS ONE POSSIBLE MECHANISM THAT UNDERLIES THE GENE X ENVIRONMENT/TREATMENT INTERACTIONS OBSERVED IN EPIDEMIOLOGICAL STUDIES AND CLINICAL TRIALS. A STUDY PUBLISHED IN BMC MEDICINE THIS MONTH BY WANG ET AL. REPORTS ON AN EXAMINATION OF DNA METHYLATION IN PERIPHERAL BLOOD LEUKOCYTES OF LEAN AND OBESE ADOLESCENTS, COMPARING METHYLATION PATTERNS BETWEEN THE TWO GROUPS. THE AUTHORS IDENTIFIED TWO GENES THAT WERE DIFFERENTIALLY METHYLATED, BOTH OF WHICH HAVE ROLES IN IMMUNE FUNCTION. HERE WE OVERVIEW THE FINDINGS FROM THIS STUDY IN THE CONTEXT OF THOSE EMERGING FROM OTHER RECENT GENETIC AND EPIGENETIC STUDIES, DISCUSS THE STRENGTHS AND WEAKNESSES OF THE STUDY AND SPECULATE ON THE FUTURE OF EPIGENETICS IN CHRONIC DISEASE RESEARCH. 2010 20 3652 22 INDIVIDUAL DNA METHYLATION PATTERN SHIFTS IN NANOPARTICLES-EXPOSED WORKERS ANALYZED IN FOUR CONSECUTIVE YEARS. A DNA METHYLATION PATTERN REPRESENTS AN ORIGINAL PLAN OF THE FUNCTION SETTINGS OF INDIVIDUAL CELLS AND TISSUES. THE BASIC STRATEGIES OF ITS DEVELOPMENT AND CHANGES DURING THE HUMAN LIFETIME ARE KNOWN, BUT THE DETAILS RELATED TO ITS MODIFICATION OVER THE YEARS ON AN INDIVIDUAL BASIS HAVE NOT YET BEEN STUDIED. MOREOVER, CURRENT EVIDENCE SHOWS THAT ENVIRONMENTAL EXPOSURE COULD GENERATE CHANGES IN DNA METHYLATION SETTINGS AND, SUBSEQUENTLY, THE FUNCTION OF GENES. IN THIS STUDY, WE ANALYZED THE EFFECT OF CHRONIC EXPOSURE TO NANOPARTICLES (NP) IN OCCUPATIONALLY EXPOSED WORKERS REPEATEDLY SAMPLED IN FOUR CONSECUTIVE YEARS (2016-2019). A DETAILED METHYLATION PATTERN ANALYSIS OF 14 PERSONS (10 EXPOSED AND 4 CONTROLS) WAS PERFORMED ON AN INDIVIDUAL BASIS. A MICROARRAY-BASED APPROACH USING CHIPS, ALLOWING THE ASSESSMENT OF MORE THAN 850 K CPG LOCI, WAS USED. INDIVIDUAL DNA METHYLATION PATTERNS WERE COMPARED BY PRINCIPAL COMPONENT ANALYSIS (PCA). THE RESULTS SHOW THE SHIFT IN DNA METHYLATION PATTERNS IN INDIVIDUAL YEARS IN ALL THE EXPOSED AND CONTROL SUBJECTS. THE OVERALL RANGE OF DIFFERENCES VARIED BETWEEN THE YEARS IN INDIVIDUAL PERSONS. THE DIFFERENCES BETWEEN THE FIRST AND LAST YEAR OF EXAMINATION (A THREE-YEAR TIME PERIOD) SEEM TO BE CONSISTENTLY GREATER IN THE NP-EXPOSED SUBJECTS IN COMPARISON WITH THE CONTROLS. THE SELECTED 14 MOST DIFFERENTLY METHYLATED CG LOCI WERE RELATIVELY STABLE IN THE CHRONICALLY EXPOSED SUBJECTS. IN SUMMARY, THE SPECIFIC TYPE OF LONG-TERM EXPOSURE CAN CONTRIBUTE TO THE FIXING OF RELEVANT EPIGENETIC CHANGES RELATED TO A SPECIFIC ENVIRONMENT AS, E.G., NP INHALATION. 2021