1 3704 119 INFLUENCE OF CIGARETTE SMOKING ON ALS OUTCOME: A POPULATION-BASED STUDY. OBJECTIVE: TO ASSESS THE PROGNOSTIC INFLUENCE OF PREMORBID SMOKING HABITS AND VASCULAR RISK PROFILE ON AMYOTROPHIC LATERAL SCLEROSIS (ALS) PHENOTYPE AND OUTCOME IN A POPULATION-BASED COHORT OF ITALIAN PATIENTS. METHODS: A TOTAL OF 650 PATIENTS WITH ALS FROM THE PIEMONTE/VALLE D'AOSTA REGISTER FOR ALS, INCIDENT IN THE 2007-2011 PERIOD, WERE RECRUITED. INFORMATION ABOUT PREMORBID CIGARETTE SMOKING HABITS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) WERE COLLECTED AT THE TIME OF DIAGNOSIS. RESULTS: CURRENT SMOKERS HAD A SIGNIFICANTLY SHORTER MEDIAN SURVIVAL (1.9 YEARS, IQR 1.2-3.4) COMPARED WITH FORMER (2.3 YEARS, IQR 1.5-4.2) AND NEVER SMOKERS (2.7 YEARS, IQR 1.8-4.6) (P=0.001). ALSO COPD ADVERSELY INFLUENCED PATIENTS' PROGNOSIS. BOTH SMOKING HABITS AND CODP WERE RETAINED IN COX MULTIVARIABLE MODEL. CONCLUSIONS: THIS STUDY HAS DEMONSTRATED IN A LARGE POPULATION-BASED COHORT OF PATIENTS WITH ALS THAT CIGARETTE SMOKING IS AN INDEPENDENT NEGATIVE PROGNOSTIC FACTOR FOR SURVIVAL, WITH A DOSE-RESPONSE GRADIENT. ITS EFFECT IS NOT RELATED TO THE PRESENCE OF COPD OR TO RESPIRATORY STATUS AT TIME OF DIAGNOSIS. THE UNDERSTANDING OF THE MECHANISMS, EITHER GENETIC OR EPIGENETIC, THROUGH WHICH EXOGENOUS FACTORS INFLUENCE DISEASE PHENOTYPE IS OF MAJOR IMPORTANCE TOWARDS A MORE FOCUSED APPROACH TO CURE ALS. 2016 2 5644 14 SEX AND THE MIGRAINE BRAIN. THE BRAIN RESPONDS DIFFERENTLY TO ENVIRONMENTAL AND INTERNAL SIGNALS THAT RELATE TO THE STAGE OF DEVELOPMENT OF NEURAL SYSTEMS. WHILE GENETIC AND EPIGENETIC FACTORS CONTRIBUTE TO A PREMORBID STATE, HORMONAL FLUCTUATIONS IN WOMEN MAY ALTER THE SET POINT OF MIGRAINE. THE CYCLIC SURGES OF GONADAL HORMONES MAY DIRECTLY ALTER NEURONAL, GLIAL AND ASTROCYTE FUNCTION THROUGHOUT THE BRAIN. ESTROGEN IS MAINLY EXCITATORY AND PROGESTERONE INHIBITORY ON BRAIN NEURONAL SYSTEMS. THESE CHANGES CONTRIBUTE TO THE ALLOSTATIC LOAD OF THE MIGRAINE CONDITION THAT MOST NOTABLY STARTS AT PUBERTY IN GIRLS. 2014 3 47 30 A CONCEPTUAL MODEL OF BIOPSYCHOSOCIAL MECHANISMS OF TRANSITION FROM ACUTE TO CHRONIC POSTSURGICAL PAIN IN CHILDREN AND ADOLESCENTS. ACUTE AND CHRONIC PAIN ARE HIGHLY PREVALENT AND IMPACTFUL CONSEQUENCES OF SURGERY ACROSS THE LIFESPAN, YET A COMPREHENSIVE CONCEPTUAL MODEL ENCOMPASSING BIOPSYCHOSOCIAL FACTORS UNDERLYING ACUTE TO CHRONIC PAIN TRANSITION IS LACKING, PARTICULARLY IN YOUTH. BUILDING ON PRIOR CHRONIC POSTSURGICAL PAIN MODELS, WE PROPOSE A NEW CONCEPTUAL MODEL OF BIOPSYCHOSOCIAL MECHANISMS OF TRANSITION FROM ACUTE TO CHRONIC POSTSURGICAL PAIN. THIS REVIEW AIMS TO SUMMARIZE EXISTING RESEARCH EXAMINING KEY FACTORS UNDERLYING ACUTE TO CHRONIC POSTSURGICAL PAIN TRANSITION IN ORDER TO GUIDE PREVENTION AND INTERVENTION EFFORTS AIMED AT ADDRESSING THIS HEALTH ISSUE IN CHILDREN. AS PAIN TRANSITIONS FROM ACUTE NOCICEPTIVE PAIN TO CHRONIC PAIN, CHANGES IN THE PERIPHERAL AND CENTRAL NERVOUS SYSTEM CONTRIBUTE TO THE CHRONIFICATION OF PAIN AFTER SURGERY. THESE CHANGES INCLUDE ALTERATIONS IN SENSORY PAIN PROCESSING AND PSYCHOSOCIAL PROCESSES (PSYCHOLOGICAL, BEHAVIORAL, AND SOCIAL COMPONENTS), WHICH PROMOTE THE DEVELOPMENT OF CHRONIC PAIN. PATIENT-RELATED PREMORBID FACTORS (EG, DEMOGRAPHIC FACTORS, GENETIC PROFILE, AND MEDICAL FACTORS SUCH AS PREMORBID PAIN) MAY FURTHER MODULATE THESE CHANGES. FACTORS RELATED TO ACUTE INJURY AND RECOVERY (EG, SURGICAL AND TREATMENT FACTORS), AS WELL AS BIOLOGICAL RESPONSE TO SURGERY (EG, EPIGENETIC, INFLAMMATORY, AND ENDOCRINE FACTORS), MAY ALSO INFLUENCE THIS PROCESS. OVERALL, LONGITUDINAL STUDIES EXAMINING TEMPORAL PATHWAYS OF BIOPSYCHOSOCIAL PROCESSES INCLUDING BOTH RISK AND RESILIENCY FACTORS WILL BE ESSENTIAL TO IDENTIFY THE MECHANISMS INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN. RESEARCH IS ALSO NEEDED TO UNRAVEL CONNECTIONS BETWEEN THE ACUTE PAIN EXPERIENCE, OPIOID EXPOSURE, AND SENSORY PAIN PROCESSING DURING ACUTE TO CHRONIC PAIN TRANSITION. FURTHERMORE, FUTURE STUDIES SHOULD INCLUDE LARGER AND MORE DIVERSE SAMPLES TO MORE FULLY EXPLORE RISK FACTORS IN A BROADER RANGE OF PEDIATRIC SURGERIES. THE USE OF CONCEPTUAL MODELS TO GUIDE INTERVENTION APPROACHES TARGETING MECHANISMS OF TRANSITION FROM ACUTE TO CHRONIC PAIN WILL SIGNIFICANTLY ADVANCE THIS FIELD AND IMPROVE OUTCOMES FOR CHILDREN AND ADOLESCENTS UNDERGOING SURGERY. 2020 4 1147 29 CONDYLE MODELING STABILITY, CRANIOFACIAL ASYMMETRY AND ACTN3 GENOTYPES: CONTRIBUTION TO TMD PREVALENCE IN A COHORT OF DENTOFACIAL DEFORMITIES. CRANIOFACIAL ASYMMETRY, MANDIBULAR CONDYLAR MODELING AND TEMPOROMANDIBULAR JOINT DISORDERS ARE COMMON COMORBIDITIES OF SKELETALLY DISPROPORTIONATE MALOCCLUSIONS, BUT ETIOLOGY OF OCCURRENCE TOGETHER IS POORLY UNDERSTOOD. WE COMPARED ASYMMETRY, CONDYLE MODELING STABILITY AND TEMPOROMANDIBULAR HEALTH IN A COHORT OF 128 PATIENTS HAVING ORTHODONTICS AND ORTHOGNATHIC SURGERY TO CORRECT DENTOFACIAL DEFORMITY MALOCCLUSIONS. WE ALSO COMPARED ACTN3 AND ENPP1 GENOTYPES FOR ASSOCIATION TO CLINICAL CONDITIONS. PRE-SURGICAL POSTERIOR-ANTERIOR CEPHALOMETRIC AND PANOMETRIC RADIOGRAPHIC ANALYSES; JAW PAIN AND FUNCTION QUESTIONNAIRE AND CLINICAL EXAMINATION OF TMD; AND SNP-GENOTYPE ANALYSIS FROM SALIVA SAMPLES WERE COMPARED TO ASSESS INTERRELATIONSHIPS. ALMOST HALF HAD ASYMMETRIES IN NEED OF SURGICAL CORRECTION, WHICH COULD BE SUBDIVIDED INTO FOUR DISTINCT MORPHOLOGICAL PATTERNS. ASYMMETRIC CONDYLE MODELING BETWEEN SIDES WAS SIGNIFICANTLY GREATER IN CRANIOFACIAL ASYMMETRY, BUT MOST COMMONLY HAD AN UNANTICIPATED PATTERN. OFTEN, LONGER OR LARGER CONDYLES OCCURRED ON THE SHORTER MANDIBULAR RAMUS SIDE. SUBJECTS WITH LONGER RAMUS BUT DIMENSIONALLY SMALLER CONDYLES WERE MORE LIKELY TO HAVE SELF-REPORTED TMD SYMPTOMS (P = 0.023) AND SIGNIFICANTLY GREATER CLINICAL DIAGNOSIS OF TMD (P = 0 .000001), WITH MASTICATORY MYALGIA MOST PROMINENT. GENOTYPING FOUND TWO SIGNIFICANT GENOTYPE ASSOCIATIONS FOR ACTN3 RS1671064 (Q523R MISSENSE) P = 0.02; RS678397 (INTRONIC SNP) P = 0.04 AND ONE SIGNIFICANT ALLELE ASSOCIATION RS1815739 (R577X NONSENSE) P = 0.00. SKELETAL ASYMMETRY, UNUSUAL CONDYLE MODELING AND TMD ARE COMMON AND INTERRELATED COMPONENTS OF MANY DENTOFACIAL DEFORMITIES. IMBALANCED MUSCULOSKELETAL FUNCTIONAL ADAPTATIONS AND GENETIC OR EPIGENETIC INFLUENCES CONTRIBUTE TO THE ETIOLOGY, AND REQUIRE FURTHER INVESTIGATION. 2020 5 5176 24 PREFACE TO COAST 2016 INNOVATORS' WORKSHOP ON PERSONALIZED AND PRECISION ORTHODONTIC THERAPY. OBJECTIVE: A SECOND FOCUSED WORKSHOP EXPLORED HOW TO TRANSFER NOVEL FINDINGS INTO CLINICAL ORTHODONTIC PRACTICE. SETTING AND SAMPLE POPULATION: PARTICIPANTS MET IN WEST PALM BEACH (FLORIDA, USA), ON 9-11 SEPTEMBER 2016 FOR THE CONSORTIUM FOR ORTHODONTIC ADVANCES IN SCIENCE AND TECHNOLOGY 2016 INNOVATORS' WORKSHOP (COAST). APPROXIMATELY 65 REGISTERED ATTENDEES CONSIDERED AND DISCUSSED INFORMATION FROM 27 TO 34 SPEAKERS, 8 TO 15 POSTER PRESENTERS AND FOUR LUNCH-HOUR FOCUS GROUP LEADERS. MATERIAL AND METHODS: THE INNOVATORS' WORKSHOPS WERE ORGANIZED ACCORDING TO FIVE THEMED SESSIONS. THE AIMS OF THE DISCUSSION SESSIONS WERE TO IDENTIFY THE FOLLOWING: I) THE STRENGTH AND IMPACT OF THE EVIDENCED-BASED DISCOVERIES, II) REQUIRED STEPS TO ENABLE FURTHER DEVELOPMENT AND III) REQUIRED STEPS TO TRANSLATE THESE NEW DISCOVERIES INTO ORTHODONTIC PRACTICE. RESULTS: THE ROLE OF GENE-ENVIRONMENT INTERACTIONS THAT UNDERLIE COMPLEX CRANIOFACIAL TRAITS WAS THE FOCUS OF SEVERAL SESSIONS. IT WAS AGREED THAT DIVERSE APPROACHES ARE CALLED FOR, SUCH AS (I) LARGE-SCALE COLLABORATIVE EFFORTS FOR FUTURE GENETIC STUDIES OF COMPLEX TRAITS; (II) DEEP GENOME SEQUENCING TO ADDRESS THE ISSUES OF ISOLATED MUTATIONS; (III) QUANTIFYING EPIGENETIC-ENVIRONMENTAL VARIABLES IN DIVERSE AREAS MYOFASCIAL PAIN, ALVEOLAR REMODELLING AND MANDIBULAR GROWTH. COMMON NEEDS IDENTIFIED FROM THE THEMED SESSIONS WERE MULTISCALE/MULTISPECIES MODELLING AND EXPERIMENTATION USING CONTROLLED AND QUANTIFIED MECHANICS AND TRANSLATION OF THE FINDINGS IN BONE BIOLOGY BETWEEN SPECIES. PANEL DISCUSSIONS LED TO THE CONSENSUS THAT A CONSORTIUM APPROACH TO ESTABLISH STANDARDS FOR INTRA-ORAL SCANNING AND 3D IMAGING SHOULD BE INITIATED. CONCLUSIONS: CURRENT AND EMERGING TECHNOLOGIES STILL REQUIRE SUPPORTED RESEARCH TO TRANSLATE NEW FINDINGS FROM THE LABORATORY TO ORTHODONTIC PRACTICE. 2017 6 5001 33 PERINATAL RISK FACTORS IN TOURETTE'S AND CHRONIC TIC DISORDERS: A TOTAL POPULATION SIBLING COMPARISON STUDY. ADVERSE PERINATAL EVENTS MAY INCREASE THE RISK OF TOURETTE'S AND CHRONIC TIC DISORDERS (TD/CTD), BUT PREVIOUS STUDIES HAVE BEEN UNABLE TO CONTROL FOR UNMEASURED ENVIRONMENTAL AND GENETIC CONFOUNDING. WE AIMED TO PROSPECTIVELY INVESTIGATE POTENTIAL PERINATAL RISK FACTORS FOR TD/CTD, TAKING UNMEASURED FACTORS SHARED BETWEEN FULL SIBLINGS INTO ACCOUNT. A POPULATION-BASED BIRTH COHORT, CONSISTING OF ALL SINGLETONS BORN IN SWEDEN IN 1973-2003, WAS FOLLOWED UNTIL DECEMBER 2013. A TOTAL OF 3 026 861 INDIVIDUALS WERE IDENTIFIED, 5597 OF WHICH HAD A REGISTERED TD/CTD DIAGNOSIS. WE THEN STUDIED DIFFERENTIALLY EXPOSED FULL SIBLINGS FROM 947 942 FAMILIES; OF THESE, 3563 FAMILIES INCLUDED SIBLINGS THAT WERE DISCORDANT FOR TD/CTD. PERINATAL DATA WERE COLLECTED FROM THE MEDICAL BIRTH REGISTER AND TD/CTD DIAGNOSES WERE COLLECTED FROM THE NATIONAL PATIENT REGISTER, USING A PREVIOUSLY VALIDATED ALGORITHM. IN THE FULLY ADJUSTED MODELS, IMPAIRED FETAL GROWTH, PRETERM BIRTH, BREECH PRESENTATION AND CESAREAN SECTION WERE ASSOCIATED WITH A HIGHER RISK OF TD/CTD, LARGELY INDEPENDENT FROM SHARED FAMILY CONFOUNDERS AND MEASURED COVARIATES. MATERNAL SMOKING DURING PREGNANCY WAS ASSOCIATED WITH RISK OF TD/CTD IN A DOSE-RESPONSE MANNER BUT THE ASSOCIATION WAS NO LONGER STATISTICALLY SIGNIFICANT IN THE SIBLING COMPARISON MODELS OR AFTER THE EXCLUSION OF COMORBID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER. A DOSE-RESPONSE RELATIONSHIP BETWEEN THE NUMBER OF ADVERSE PERINATAL EVENTS AND INCREASED RISK FOR TD/CTD WAS ALSO OBSERVED, WITH HAZARD RATIOS RANGING FROM 1.41 (95% CONFIDENCE INTERVAL (CI): 1.33-1.50) FOR ONE EVENT TO 2.42 (95% CI: 1.65-3.53) FOR FIVE OR MORE EVENTS. THESE RESULTS PAVE THE WAY FOR FUTURE GENE BY ENVIRONMENT INTERACTION AND EPIGENETIC STUDIES IN TD/CTD. 2018 7 6785 22 [CONFLICT MEDIATION: AN ADDITIONAL OPTION FOR THE MEDICAL PRACTITIONER]. CHRONIC STRESS AFFECTS THE INDIVIDUAL AND OFFSPRING THROUGH A COMBINATION OF SOCIAL, GENETIC AND EPIGENETIC FACTORS THAT PREDISPOSE TO VARIOUS ILLNESSES. FURTHERMORE, CONFLICT UNFAVORABLY AFFECTS MENTALIZATION WHICH WOULD HELP ITS RESOLUTION. THE PSYCHOPHYSIOLOGICAL PARAMETERS OF STRESS DROP WHEN AN INDIVIDUAL GOES FROM THE STATE OF UNFORGIVENESS TO THAT OF FORGIVENESS AND THIS IS COMPARABLE TO THE FEELING OF RELIEF EXPERIENCED AFTER A SUCCESSFUL MEDIATION. THE AUTHOR BRIEFLY ILLUSTRATES CONFLICT MEDIATION FROM A PSYCHODYNAMIC POINT OF VIEW. THE MEDIATION PROCESS INSCRIBES ITSELF IN A PROLONGATION OF FREUD'S KULTURARBEIT. THE AUTHOR CONCLUDES THAT THE MEDICAL PRACTITIONER COULD IDENTIFY PATIENTS WHOSE AILMENTS ARE DIRECTLY RELATED TO EXPERIENCING RECENT CONFLICT AND FOR WHOM CONFLICT MEDIATION COULD PROVE TO BE BENEFICIAL. 2022 8 5776 21 SPHN - THE SWISS AGING CITIZEN REFERENCE (SACR). IN SWITZERLAND BY 2045, WE EXPECT 2.7 MIO CITIZENS AGED 65+ OF WHOM 1.0 MIO. AGED 80+. A PRIORITY AND FOCUS OF PERSONALIZED HEALTH RESEARCH IS THEREFORE AGING BIOLOGY TO EXTEND HEALTHY LIFE EXPECTANCY. NOVEL MOLECULAR AND IMAGING FEATURES WILL EMERGE AS CANDIDATE TARGETS FOR RISK PREDICTION AND SCREENING OF CHRONIC DISEASES. IT IS OF UTMOST IMPORTANCE TO TEST THE CLINICAL AND PUBLIC HEALTH UTILITY OF CANDIDATE BIOMARKERS EVOLVING FROM THIS RESEARCH IN CITIZEN REFERENCE COHORTS. WE WILL BUILD A SWISS AGING CITIZEN REFERENCE (SACR), A TESTABLE AND SCALABLE REFERENCE COHORT OFFERING INTEROPERABLE, SEARCHABLE, AND ACCESSIBLE DATA. 1000 PARTICIPANTS FROM EXISTING SWISS CITIZEN COHORTS WILL BE COMBINED AND ANALYZED FOR DNA METHYLATION AND MRI BRAIN IMAGING. SACR WILL SERVE AS A TESTBED FOR CLINICAL AND PUBLIC HEALTH UTILITY OF CANDIDATE BIOMARKERS. AS FOR A PROOF-OF-CONCEPT STUDY, WE WILL CONDUCT AN AGNOSTIC SEARCH FOR STRUCTURAL AND FUNCTIONAL BRAIN FEATURES ASSOCIATED WITH EPIGENETIC AGING ACCELERATION TO EXAMINE THE POTENTIAL OF EPIGENETIC AGE ACCELERATION AS THE INTERMEDIATE AGING BIOMARKER AND TO BETTER UNDERSTAND THE AGING MECHANISM IN BRAIN. 2020 9 6507 13 TRAINING VOCATIONAL REHABILITATION COUNSELORS WHO WORK WITH CHRONIC MENTAL PATIENTS. BECAUSE OF THE INEFFICACY OF DISPARATE PSYCHIATRIC AND REHABILITATIVE APPROACHES TO PSYCHOSOCIAL RESTORATION OF CHRONIC MENTAL PATIENTS, THE AUTHORS DESIGNED THE NEW ENGLAND PSYCHIATRIC REHABILITATION TRAINING PROGRAM FOR VOCATIONAL REHABILITATION COUNSELORS WHO WORK WITH THESE PATIENTS. THE PROGRAM EXTENDS ERIKSON'S EPIGENETIC SEQUENCE TO DEVELOPMENT OF WORK CAPACITY AND EMPHASIZES A COMPREHENSIVE, MULTIAXIAL APPROACH TO PSYCHOPATHOLOGY AND VOCATIONAL REHABILITATION. AFTER 6 WEEKS OF SEMINARS, CLINICAL WORK, AND SUPERVISION, COUNSELORS RETURN TO THEIR AGENCIES AND RECEIVE AN ADDITIONAL 8 WEEKS OF PART-TIME SUPPORT FROM FIELD FACULTY INSTRUCTORS. 1981 10 645 28 BIRTH DEFECTS IN GAZA: PREVALENCE, TYPES, FAMILIARITY AND CORRELATION WITH ENVIRONMENTAL FACTORS. THIS IS THE FIRST REPORT OF REGISTRATION AT BIRTH, AND OF INCIDENCE OF MAJOR STRUCTURAL BIRTH DEFECTS (BD) OBTAINED IN GAZA AT AL SHIFA HOSPITAL, WHERE 28% OF TOTAL BIRTHS IN GAZA STRIP OCCUR. DOCTORS REGISTERED 4,027 DELIVERIES, WITH A PROTOCOL COMPREHENSIVE OF CLINICAL, DEMOGRAPHIC, KIN AND ENVIRONMENTAL QUESTIONS. PREVALENCE OF BD IS 14/1,000, WITHOUT ASSOCIATION WITH INTERMARRIAGE OR GENDER OF THE CHILD. PREVALENCE OF LATE MISCARRIAGES AND STILL BIRTHS ARE RESPECTIVELY 23.3/1,000 AND 7.4/1,000, AND OF PREMATURE BIRTHS 19.6/1,000. COUPLES WITH A BD CHILD HAVE ABOUT 10 TIMES HIGHER FREQUENCY OF RECURRENCE OF A BD IN THEIR PROGENY THAN THOSE WITH NORMAL CHILDREN, BUT NONE OF THEIR 694 SIBLINGS AND ONLY 10/1,000 OF THEIR 1,423 PROGENY HAD BD, SIMILAR TO THE FREQUENCY IN GENERAL POPULATION. THESE DATA SUGGEST OCCURRENCE OF NOVEL GENETIC AND EPIGENETIC EVENTS IN DETERMINATION OF BD. CHILDREN WITH BD WERE BORN WITH HIGHER FREQUENCY (P < 0 001) IN FAMILIES WHERE ONE OR BOTH PARENTS WERE UNDER "WHITE PHOSPHORUS" ATTACK, THAT IN THE GENERAL POPULATION. BOMBING OF THE FAMILY HOME AND REMOVAL OF THE RUBBLE WERE ALSO FREQUENTLY REPORTED BY COUPLES WITH BD OCCURRENCE. THESE DATA SUGGESTS A CAUSATIVE/FAVORING ROLE OF ACUTE EXPOSURE OF PARENTS TO THE WEAPONS-ASSOCIATED CONTAMINANTS, AND/OR OF THEIR CHRONIC EXPOSURE FROM THEIR PERSISTENCE IN THE ENVIRONMENT ON THE EMBRYONIC DEVELOPMENT OF THEIR CHILDREN. 2012 11 2858 30 FROM RILUZOLE TO DEXPRAMIPEXOLE VIA SUBSTITUTED-BENZOTHIAZOLE DERIVATIVES FOR AMYOTROPHIC LATERAL SCLEROSIS DISEASE TREATMENT: CASE STUDIES. THE 1,3-BENZOTHIAZOLE (BTZ) RING MAY OFFER A VALID OPTION FOR SCAFFOLD-HOPPING FROM INDOLE DERIVATIVES. SEVERAL BTZS HAVE CLINICALLY RELEVANT ROLES, MAINLY AS CNS MEDICINES AND DIAGNOSTIC AGENTS, WITH RILUZOLE BEING ONE OF THE MOST FAMOUS EXAMPLES. RILUZOLE IS CURRENTLY THE ONLY APPROVED DRUG TO TREAT AMYOTROPHIC LATERAL SCLEROSIS (ALS) BUT ITS EFFICACY IS MARGINAL. SEVERAL CLINICAL STUDIES HAVE DEMONSTRATED ONLY LIMITED IMPROVEMENTS IN SURVIVAL, WITHOUT BENEFITS TO MOTOR FUNCTION IN PATIENTS WITH ALS. DESPITE SIGNIFICANT CLINICAL TRIAL EFFORTS TO UNDERSTAND THE GENETIC, EPIGENETIC, AND MOLECULAR PATHWAYS LINKED TO ALS PATHOPHYSIOLOGY, THERAPEUTIC TRANSLATION HAS REMAINED DISAPPOINTINGLY SLOW, PROBABLY DUE TO THE COMPLEXITY AND THE HETEROGENEITY OF THIS DISEASE. MANY OTHER DRUGS TO TACKLE ALS HAVE BEEN TESTED FOR 20 YEARS WITHOUT ANY SUCCESS. DEXPRAMIPEXOLE IS A BTZ STRUCTURAL ANALOG OF RILUZOLE AND WAS A GREAT HOPE FOR THE TREATMENT OF ALS. IN THIS REVIEW, AS AN INTERESTING CASE STUDY IN THE DEVELOPMENT OF A NEW MEDICINE TO TREAT ALS, WE PRESENT THE STRATEGY OF THE DEVELOPMENT OF DEXPRAMIPEXOLE, WHICH WAS ONE OF THE MOST PROMISING DRUGS AGAINST ALS. 2020 12 5137 30 POTENTIAL MECHANISMS OF NON-SUICIDAL SELF-INJURY (NSSI) IN MAJOR DEPRESSIVE DISORDER: A SYSTEMATIC REVIEW. BACKGROUND: NON-SUICIDAL SELF-INJURY (NSSI) IS A FREQUENT AND PROMINENT PHENOMENON IN MAJOR DEPRESSIVE DISORDER (MDD). EVEN THOUGH ITS PREVALENCE AND RISK FACTORS ARE RELATIVELY WELL UNDERSTOOD, THE POTENTIAL MECHANISMS OF NSSI IN MDD REMAIN ELUSIVE. AIMS: TO REVIEW PRESENT EVIDENCE RELATED TO THE POTENTIAL MECHANISMS OF NSSI IN MDD. METHODS: ACCORDING TO PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES 2020 GUIDELINES, ARTICLES FOR THIS SYSTEMATIC REVIEW WERE SEARCHED ON MEDLINE (THROUGH PUBMED), EMBASE (THROUGH ELSEVIER), PSYCINFO (THROUGH OVID) AND WEB OF SCIENCE DATABASES FOR ENGLISH ARTICLES, AS WELL AS CHINA NATIONAL KNOWLEDGE INFRASTRUCTURE (CNKI), SINOMED, WANFANG DATA, AND THE CHONGQING VIP CHINESE SCIENCE AND TECHNOLOGY PERIODICAL (VIP) DATABASES FOR CHINESE ARTICLES PUBLISHED FROM THE DATE OF INCEPTION TO 2 AUGUST 2022. TWO RESEARCHERS (BW, HZ) INDEPENDENTLY SCREENED STUDIES BASED ON INCLUSION AND EXCLUSION CRITERIA AND ASSESSED THEIR QUALITY. RESULTS: A TOTAL OF 25 157 STUDIES WERE SEARCHED. ONLY 25 OF THEM WERE ULTIMATELY INCLUDED, CONTAINING 3336 SUBJECTS (1535 PATIENTS WITH MDD AND NSSI, 1403 PATIENTS WITH MDD WITHOUT NSSI AND 398 HCS). INCLUDED STUDIES WERE DIVIDED INTO 6 CATEGORIES: PSYCHOSOCIAL FACTORS (11 STUDIES), NEUROIMAGING (8 STUDIES), STRESS AND HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS (2 STUDIES), PAIN PERCEPTION (1 STUDY), ELECTROENCEPHALOGRAM (EEG) (2 STUDIES) AND EPIGENETICS (1 STUDY). CONCLUSIONS: THIS SYSTEMATIC REVIEW INDICATES THAT PATIENTS WITH MDD AND NSSI MIGHT HAVE SPECIFIC PSYCHOSOCIAL FACTORS, ABERRANT BRAIN FUNCTIONS AND NEUROCHEMICAL METABOLISMS, HPA AXIS DYSFUNCTIONS, ABNORMAL PAIN PERCEPTIONS AND EPIGENETIC ALTERATIONS. 2023 13 2096 31 EPIGENETIC EFFECTS OF CHILDHOOD ADVERSITY IN THE BRAIN AND SUICIDE RISK. WITH PREVALENCE ESTIMATES RANGING BETWEEN 6.4% AND 10.1% [-5], MAJOR DEPRESSION RANKS FIRST AMONG THE MOST SIGNIFICANT CAUSES OF DISABILITY AND PREMATURE DEATH, THUS IMPOSING A CONTINUAL ECONOMIC BURDEN ON SOCIETY. FOR INSTANCE, IN THE UNITED STATES, THE DIRECT AND INDIRECT COSTS ARE ESTIMATED AT U.S.$44 BILLION/YEAR [6]. THE GREATEST LOSS TO OUR SOCIETY, HOWEVER, IS THE ASSOCIATED MORTALITY BY SUICIDE RELATED TO MAJOR DEPRESSION. INDEED, IT HAS BEEN ESTIMATED THAT BETWEEN 50% AND 70% OF SUICIDE COMPLETERS WILL DIE DURING AN EPISODE OF MAJOR DEPRESSION [7,8] AND PROSPECTIVE FOLLOW-UP STUDIES OF MAJOR DEPRESSION SUGGEST THAT BETWEEN 7% AND 15% OF THESE PATIENTS WILL DIE BY SUICIDE [-12]. SUICIDE IS A COMPLEX PROBLEM, WHICH IS BELIEVED TO RESULT FROM THE INTERACTION OF SEVERAL DIFFERENT FACTORS [13,14]. INDEED, PSYCHOLOGICAL FACTORS AND PERSONALITY TRAITS SUCH AS IMPULSIVITY AND NEGATIVE AFFECT [14,15], SOCIAL FACTORS [16,17], ENVIRONMENTAL FACTORS SUCH AS EARLY-LIFE ADVERSITY [-20], GENETIC FACTORS [21], AND NEUROBIOLOGICAL FACTORS [22] HAVE BEEN PROPOSED TO INDUCE BEHAVIORAL ALTERATIONS, WHICH IN TURN MAY PREDISPOSE CERTAIN INDIVIDUALS TO DEVELOP DEPRESSIVE AND SUICIDAL BEHAVIORS. HOWEVER, SINCE THESE FACTORS ALONE ARE UNLIKELY TO EXPLAIN SUICIDE AND SUICIDE RISK, IT MAY BE MORE READILY EXPLAINED WHEN CONSIDERING THE INTERACTION BETWEEN THESE DIFFERENT SOURCES OF VARIATION [23,24]. AMONG THESE RISK FACTORS, EARLY-LIFE ADVERSITY, PARTICULARLY CHILDHOOD SEXUAL ABUSE (CSA) AND CHILDHOOD PHYSICAL ABUSE (CPA), IS ONE OF THE STRONGEST PREDICTORS OF MENTAL DISORDERS [25,26] AND SUICIDE [18,19]. FOR EXAMPLE, STUDIES HAVE SHOWN THAT CSA IS ASSOCIATED WITH EARLY ONSET OF DEPRESSION, CHRONIC COURSE, AND MORE SEVERE DEPRESSIVE OUTCOME [-29] BUT, MORE IMPORTANTLY, WITH 12 TIMES HIGHER ODDS OF SUICIDAL BEHAVIORS [26,30]. ALTHOUGH LESS CONSISTENTLY, CPA AND NEGLECT HAVE ALSO BEEN ASSOCIATED WITH SUICIDAL BEHAVIORS [19,31]. CSA AND CPA HAVE BEEN ASSOCIATED WITH HIGHER ODDS OF SELF-HARM [,,-34], SUICIDAL IDEATION [35,36], AND SUICIDE ATTEMPTS [,-39]. MOREOVER, THE PREVALENCE OF SUICIDAL IDEATION AND SUICIDE ATTEMPTS HAS BEEN SHOWN TO INCREASE WITH THE SEVERITY AND INTENSITY OF THE ABUSE [35,36,38]. 2012 14 4067 19 MATERNAL AND PEDIATRIC HEALTH AND DISEASE: INTEGRATING BIOPSYCHOSOCIAL MODELS AND EPIGENETICS. THE CONCEPTS OF ALLOSTASIS (STABILITY THROUGH ADAPTATION) AND ACCUMULATED LIFE STRESS (MCEWEN'S ALLOSTATIC LOAD) AIM TO UNDERSTAND CHILDHOOD AND ADULT OUTCOMES. CHRONIC MALNUTRITION, CHANGES IN SOCIAL CONDITION, AND ADVERSE EARLY-LIFE EXPERIENCES MAY PROGRAM PHENOTYPES AND CONTRIBUTE TO LONG-LASTING DISEASE RISK. HOWEVER, INTEGRATION OF LIFE COURSE APPROACHES, SOCIAL AND ECONOMIC CONTEXTS, AND COMPARISON AMONG DIFFERENT BIOPSYCHOSOCIAL MODELS HAS NOT GENERALLY BEEN EXPLORED. THIS REVIEW CRITICALLY EXAMINES THE LITERATURE AND EVALUATES RECENT INSIGHTS INTO HOW ENVIRONMENTAL STRESS CAN ALTER LIFELONG HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND IMMUNE SYSTEM RESPONSIVENESS AND INDUCE METABOLIC AND NEURODEVELOPMENTAL MALADAPTATION. MODELS OF BIOPSYCHOSOCIAL STRESS OVERLAP BUT MAY CONSIDER DIFFERENT CONDITIONS. CONCEPTS INCLUDE ALLOSTASIS, WHICH INCORPORATES HORMONAL RESPONSES TO PREDICTABLE ENVIRONMENTAL CHANGES, AND GERONIMUS'S "WEATHERING," WHICH AIMS TO EXPLAIN HOW SOCIALLY STRUCTURED, REPEATED STRESS CAN ACCUMULATE AND INCREASE DISEASE VULNERABILITY. WEATHERING EMPHASIZES ROLES OF INTERNALIZED/INTERPERSONAL RACISM IN OUTCOMES DISPARITIES. FOR MEXICAN IMMIGRANTS AND MEXICAN AMERICANS, THE "ACCULTURATION" FRAMEWORK HAS PROVEN ESPECIALLY USEFUL TO EXPLORE DISPARITIES, INCLUDING PRETERM BIRTH AND NEUROPSYCHIATRIC RISKS IN CHILDHOOD. COMPLEXITIES OF STRESS ASSESSMENTS AND RECENT RESEARCH INTO EPIGENETIC MECHANISMS MEDIATING EFFECTS OF PHYSICAL, NUTRITIONAL, PSYCHOLOGICAL, AND SOCIAL STRESS ARE REVIEWED. 2016 15 6914 29 [VITAMIN D DEFICIENCY IN PREGNANCY AND ITS IMPACT ON THE FETUS, THE NEWBORN AND IN CHILDHOOD]. OBJECTIVE: VITAMIN D DEFICIENCY (VDD) IN PREGNANT WOMEN AND THEIR CHILDREN IS AN IMPORTANT HEALTH PROBLEM WITH SEVERE CONSEQUENCES FOR THE HEALTH OF BOTH. THUS, THE OBJECTIVES OF THIS REVIEW WERE TO REASSESS THE MAGNITUDE AND CONSEQUENCES OF VDD DURING PREGNANCY, LACTATION AND INFANCY, ASSOCIATED RISK FACTORS, PREVENTION METHODS, AND TO EXPLORE EPIGENETIC MECHANISMS IN EARLY FETAL LIFE CAPABLE OF EXPLAINING MANY OF THE NON-SKELETAL BENEFITS OF VITAMIN D (VID). DATA SOURCE: ORIGINAL AND REVIEW ARTICLES, AND CONSENSUS DOCUMENTS WITH ELEVATED LEVEL OF EVIDENCE FOR VDD-RELATED CLINICAL DECISIONS ON THE HEALTH OF PREGNANT WOMEN AND THEIR CHILDREN, AS WELL AS ARTICLES ON THE INFLUENCE OF VID ON EPIGENETIC MECHANISMS OF FETAL PROGRAMMING OF CHRONIC DISEASES IN ADULTHOOD WERE SELECTED AMONG ARTICLES PUBLISHED ON PUBMED OVER THE LAST 20 YEARS, USING THE SEARCH TERM VITD STATUS, IN COMBINATION WITH PREGNANCY, OFFSPRING HEALTH, CHILD OUTCOMES, AND PROGRAMMING. DATA SYNTHESIS: THE FOLLOWING ITEMS WERE ANALYZED: VID PHYSIOLOGY AND METABOLISM, RISK FACTORS FOR VDD AND IMPLICATIONS IN PREGNANCY, LACTATION AND INFANCY, CONCENTRATION CUTOFF TO DEFINE VDD, THE VARIABILITY OF METHODS FOR VDD DETECTION, RECOMMENDATIONS ON VID REPLACEMENT IN PREGNANT WOMEN, THE NEWBORN AND THE CHILD, AND THE EPIGENETIC INFLUENCE OF VID. CONCLUSIONS: VDD IS A COMMON CONDITION AMONG HIGH-RISK PREGNANT WOMEN AND THEIR CHILDREN. THE ROUTINE MONITORING OF SERUM 25(OH)D3 LEVELS IN ANTENATAL PERIOD IS MANDATORY. EARLY PREVENTIVE MEASURES SHOULD BE TAKEN AT THE SLIGHTEST SUSPICION OF VDD IN PREGNANT WOMEN, TO REDUCE MORBIDITY DURING PREGNANCY AND LACTATION, AS WELL AS ITS SUBSEQUENT IMPACT ON THE FETUS, THE NEWBORN AND THE CHILD. 2015 16 4492 29 MONOZYGOTIC TWINS DISCORDANT FOR ROHHAD PHENOTYPE. RAPID-ONSET OBESITY WITH HYPOTHALAMIC DYSFUNCTION, HYPOVENTILATION, AND AUTONOMIC DYSREGULATION (ROHHAD) FALLS WITHIN A GROUP OF PEDIATRIC DISORDERS WITH BOTH RESPIRATORY CONTROL AND AUTONOMIC NERVOUS SYSTEM DYSREGULATION. CHILDREN WITH ROHHAD TYPICALLY PRESENT AFTER 1.5 YEARS OF AGE WITH RAPID WEIGHT GAIN AS THE INITIAL SIGN. SUBSEQUENTLY, THEY DEVELOP ALVEOLAR HYPOVENTILATION, AUTONOMIC NERVOUS SYSTEM DYSREGULATION, AND, IF UNTREATED, CARDIORESPIRATORY ARREST. TO OUR KNOWLEDGE, THIS IS THE FIRST REPORT OF DISCORDANT PRESENTATION OF ROHHAD IN MONOZYGOTIC TWINS. TWIN GIRLS, BORN AT TERM, HAD CONCORDANT GROWTH AND DEVELOPMENT UNTIL 8 YEARS OF AGE. FROM 8 TO 12 YEARS OF AGE, THE AFFECTED TWIN DEVELOPED FEATURES CHARACTERISTIC OF ROHHAD INCLUDING OBESITY, ALVEOLAR HYPOVENTILATION, SCOLIOSIS, HYPOTHALAMIC DYSFUNCTION (CENTRAL DIABETES INSIPIDUS, HYPOTHYROIDISM, PREMATURE PUBARCHE, AND GROWTH HORMONE DEFICIENCY), RIGHT PARASPINAL/THORACIC GANGLIONEUROBLASTOMA, SEIZURES, AND AUTONOMIC DYSREGULATION INCLUDING ALTERED PAIN PERCEPTION, LARGE AND SLUGGISHLY REACTIVE PUPILS, HYPOTHERMIA, AND PROFOUND BRADYCARDIA THAT REQUIRED A CARDIAC PACEMAKER. RESULTS OF GENETIC TESTING FOR PHOX2B (CONGENITAL CENTRAL HYPOVENTILATION SYNDROME DISEASE-DEFINING GENE) MUTATIONS WERE NEGATIVE. WITH EARLY RECOGNITION AND CONSERVATIVE MANAGEMENT, THE AFFECTED TWIN HAD EXCELLENT NEUROCOGNITIVE OUTCOME THAT MATCHED THAT OF THE UNAFFECTED TWIN. THE UNAFFECTED TWIN DEMONSTRATED RAPID WEIGHT GAIN LATER IN AGE BUT NOT DEVELOPMENT OF SIGNS/SYMPTOMS CONSISTENT WITH ROHHAD. THIS DISCORDANT TWIN PAIR DEMONSTRATES KEY FEATURES OF ROHHAD INCLUDING THE IMPORTANCE OF EARLY RECOGNITION (ESPECIALLY HYPOVENTILATION), COMPLEXITY OF SIGNS/SYMPTOMS AND CLINICAL COURSE, AND IMPORTANCE OF INITIATING COMPREHENSIVE, MULTISPECIALTY CARE. THESE CASES CONFOUND THE HYPOTHESIS OF A MONOGENIC ETIOLOGY FOR ROHHAD AND INDICATE ALTERNATIVE ETIOLOGIES INCLUDING AUTOIMMUNE OR EPIGENETIC PHENOMENON OR A COMBINATION OF GENETIC PREDISPOSITION AND ACQUIRED PRECIPITANT. 2011 17 4465 28 MOLECULAR MECHANISMS OF POSTTRAUMATIC STRESS DISORDER (PTSD) AS A BASIS FOR INDIVIDUALIZED AND PERSONALIZED THERAPY: RATIONALE, DESIGN AND METHODS OF THE SOUTH EASTERN EUROPE (SEE)-PTSD STUDY. POSTTRAUMATIC STRESS DISORDER (PTSD) IS A MAJOR HEALTH PROBLEM IN SOUTH EASTERN EUROPE (SEE). AVAILABLE TREATMENT OPTIONS ARE NOT EFFICIENT ENOUGH AND THE COURSE IS OFTEN CHRONIC. LITTLE IS KNOWN ABOUT MOLECULAR MEDIATORS AND MODERATORS OF PATHOGENESIS AND THERAPY. GENETIC AND EPIGENETIC VARIATION MAY BE ONE CENTRAL MOLECULAR MECHANISM. WE THEREFORE ESTABLISHED A CONSORTIUM COMBINING CLINICAL EXPERTISE ON PTSD FROM SEE COUNTRIES BOSNIA-HERZEGOVINA (SARAJEVO, TUZLA AND MOSTAR), KOSOVO (PRISHTINA) AND CROATIA (ZAGREB) WITH GENETIC AND EPIGENETIC COMPETENCE FROM GERMANY (WURZBURG) IN 2011 WITHIN THE FRAMEWORK OF THE DAAD (DEUTSCHER AKADEMISCHER AUSTAUSCHDIENST)-FUNDED STABILITY PACT FOR SOUTH EASTERN EUROPE. AFTER OBTAINING ETHICAL VOTES AND PERFORMING RATER TRAININGS AS WELL AS TRAINING IN DNA EXTRACTION FROM EDTA BLOOD BETWEEN 2011 AND 2013, WE RECRUITED 747 INDIVIDUALS WHO HAD EXPERIENCED WAR-RELATED TRAUMA IN THE SEE CONFLICTS BETWEEN 1991 AND 1999. 236 PARTICIPANTS HAD CURRENT PTSD, 161 LIFETIME PTSD AND 350 DID NOT HAVE AND NEVER HAD PTSD. DEMOGRAPHIC AND CLINICAL DATA ARE CURRENTLY MERGED TOGETHER WITH GENETIC AND EPIGENETIC DATA IN A SINGLE DATABASE TO ALLOW FOR A COMPREHENSIVE ANALYSIS OF THE ROLE OF GENETIC AND EPIGENETIC VARIATION IN THE PATHOGENESIS AND THERAPY OF PTSD. ANALYSES WILL BE DONE TO A GREAT DEGREE BY PHD STUDENTS FROM PARTICIPATING SEE CENTERS WHO IN ADDITION TO PARTICIPATION IN THE PROJECT HAD AN OPPORTUNITY TO TAKE PART IN SPRING AND SUMMER SCHOOLS OF THE DFG (DEUTSCHE FORSCHUNGSGEMEINSCHAFT) FUNDED RESEARCH TRAINING GROUP (RTG) 1253 AND THUS MEET PHD STUDENTS FROM GERMANY AND OTHER COUNTRIES WE ARE CONFIDENT THAT OUR PROJECT WILL NOT ONLY CONTRIBUTE TO A BETTER UNDERSTANDING OF GENETIC AND EPIGENETIC MECHANISMS OF PTSD AS A BASIS FOR FUTURE INDIVIDUALIZED AND PERSONALIZED THERAPIES, BUT ALSO TO THE ACADEMIC DEVELOPMENT OF SOUTH EASTERN EUROPE. 2016 18 4986 32 PATIENT-REPORTED SYMPTOM OUTCOMES AND MICROSATELLITE INSTABILITY IN PATIENTS WITH METASTATIC COLORECTAL CANCER. BACKGROUND: THE SURVIVAL OF PATIENTS WITH METASTATIC COLORECTAL CANCER (MCRC) IS INFLUENCED BY THE GENETIC AND EPIGENETIC CHANGES THAT MIGHT INFLUENCE THE PATIENT EXPERIENCE OF SYMPTOM BURDEN. UNDERSTANDING THE ASSOCIATION OF MOLECULAR CHANGES WITH THE SYMPTOM BURDEN COULD HELP CLINICIANS GAIN INSIGHT INTO THE MOLECULAR BASIS OF SYMPTOM BURDEN AND IMPROVE TREATMENT TOLERANCE. TO DATE, NO STUDIES HAVE COMPARED THE PATIENT-REPORTED SYMPTOM BURDEN WITH THESE MOLECULAR SUBSETS AMONG PATIENTS WITH MCRC. PATIENTS AND METHODS: WE RECRUITED PATIENTS WITH MCRC THAT WAS REFRACTORY TO >/= 1 LINE OF THERAPY WHO HAD BEEN ENROLLED IN THE ASSESSMENT OF TARGETED THERAPIES AGAINST COLORECTAL CANCER TRIAL AT THE UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER. ALL PATIENTS COMPLETED A BASELINE GASTROINTESTINAL SYMPTOM INVENTORY (MD ANDERSON SYMPTOM INVENTORY, GASTROINTESTINAL). THE SYMPTOM BURDEN ACROSS KEY DEMOGRAPHIC VARIABLES AND MOLECULAR CHANGES, INCLUDING CRC-ASSOCIATED MUTATIONS, MICROSATELLITE INSTABILITY (MSI) STATUS, AND THE CPG ISLAND METHYLATOR PHENOTYPE (CIMP) WERE COMPARED USING CHI(2) TESTS. ASSOCIATION OF THE SYMPTOM BURDEN WITH OVERALL SURVIVAL WAS EXAMINED USING COX REGRESSION MODELS. RESULTS: PATIENTS WITH AN MSI-HIGH (MSI-H) PHENOTYPE REPORTED GREATER PAIN (ODDS RATIO [OR], 3.06; 95% CONFIDENCE INTERVAL [CI], 1.61-5.84), FATIGUE (OR, 2.78; 95% CI, 1.41-5.49), SLEEP (OR, 2.52; 95% CI, 1.32-4.08); AND DROWSINESS (OR, 2.51; 95% CI, 1.32-4.78) COMPARED WITH MICROSATELLITE STABLE PATIENTS. PATIENTS WITH AN MSI-H PHENOTYPE ALSO HAD GREATER ODDS OF OVERALL SYMPTOM BURDEN (OR, 2.48; 95% CI, 1.29-4.74) COMPARED WITH MICROSATELLITE STABLE PATIENTS. THE CIMP-HIGH PATIENTS EXPERIENCED GREATER ODDS OF PAIN COMPARED WITH THE CIMP-NEGATIVE PATIENTS (OR, 1.72; 95% CI, 1.06-2.80). A GREATER OVERALL SYMPTOM BURDEN WAS ASSOCIATED WITH POOR OVERALL SURVIVAL (HAZARD RATIO, 1.42; 95% CI, 0.98-2.06]), ALTHOUGH THE DIFFERENCE WAS NOT SIGNIFICANT (P = .06). CONCLUSION: CORRELATION OF MSI-H-ASSOCIATED TUMOR FEATURES WITH THE SYMPTOM BURDEN COULD HELP PROVIDE A BETTER UNDERSTANDING OF UNDERLYING MECHANISMS ASSOCIATED WITH OUR FINDINGS. 2020 19 5958 22 TELOMERE LENGTH AND SALIVARY CORTISOL STRESS REACTIVITY IN VERY PRETERM INFANTS. DURING THE NEONATAL INTENSIVE CARE UNIT (NICU) STAY, VERY PRETERM (VPT) INFANTS ARE EXPOSED TO LIFE-SAVING YET PAIN-INDUCING SKIN-BREAKING PROCEDURES (I.E., NICU PAIN-RELATED STRESS) WHICH CONTRIBUTE TO THE PROGRAMMING OF HYPO-RESPONSIVE HPA AXIS DEVELOPMENT DURING THE FIRST MONTHS OF LIFE. UNFORTUNATELY, TO DATE THE MECHANISMS LINKING NICU PAIN-RELATED STRESS AND ALTERED HPA AXIS REGULATION ARE ONLY LIMITEDLY KNOWN. TELOMERE LENGTH (TL) REGULATION IS AN EPIGENETIC MECHANISM PREVIOUSLY SHOWN TO BE AFFECTED BY EARLY STRESS EXPOSURES AND CAPABLE OF ASSOCIATING WITH HPA AXIS REACTIVITY IN CHILDREN. IN VPT INFANTS, NICU PAIN-RELATED STRESS WAS FOUND TO ASSOCIATE WITH DECREASED TL FROM BIRTH TO DISCHARGE, BUT THERE IS NO EVIDENCE FOR THE ASSOCIATION BETWEEN TL AND HPA AXIS IN THESE INFANTS. IN THIS STUDY, WE PROSPECTIVELY EXAMINED THE RELATIONSHIP BETWEEN NICU PAIN-RELATED STRESS AND HPA AXIS REACTIVITY TO AN AGE-APPROPRIATE SOCIO-EMOTIONAL CONDITION (I.E., THE STILL-FACE PROCEDURE, SFP) IN HEALTHY VPT INFANTS AT 3-MONTH CORRECTED AGE. NICU PAIN-RELATED STRESS WAS COMPUTED AS THE RATIO BETWEEN THE NUMBER OF SKIN-BREAKING PROCEDURES AND LENGTH OF NICU STAY. A DIFFERENTIAL SCORE (I.E., ?TL) WAS OBTAINED SUBTRACTING TL AT BIRTH FROM TL AT DISCHARGE. A NORMALIZED (LOG10) CORTISOL REACTIVITY INDEX (CRI) WAS OBTAINED BY AVERAGING POST-STRESS (20 MIN AFTER SFP) SALIVARY CORTISOL SAMPLE ON BASELINE VALUE. A REGRESSION MODEL CONTROLLING FOR NEONATAL AND SOCIO-DEMOGRAPHIC CONFOUNDERS SHOWED THAT ?TL WAS THE ONLY SIGNIFICANT PREDICTOR OF CRI. ALTHOUGH PRELIMINARY, THESE FINDINGS CONTRIBUTE TO OUR KNOWLEDGE OF THE MECHANISMS LINKING EARLY EXPOSURES TO ADVERSITY AND LATER IN LIFE REGULATION OF THE HPA AXIS IN VPT INFANTS. 2019 20 6433 24 THE VINDICATION OF LAMARCK? EPIGENETICS AT THE INTERSECTION OF LAW AND MENTAL HEALTH. RESEARCH ON EPIGENETIC MECHANISMS IS GAINING TRACTION, YET IS POORLY UNDERSTOOD BY CRIMINOLOGISTS AND BEHAVIORAL SCIENTISTS. THE CURRENT OBJECTIVE IS TO REVIEW RELEVANT STUDIES OF INTEREST TO BEHAVIORAL SCIENTISTS WHO STUDY CRIME, AND TO TRANSLATE ADMITTEDLY CHALLENGING SCIENTIFIC INFORMATION INTO TEXT THAT IS DIGESTIBLE TO THE AVERAGE CRIMINOLOGIST. USING SYSTEMATIC SEARCH PROCEDURES THE AUTHORS IDENTIFIED AND REVIEWED 41 STUDIES OF EPIGENETIC MECHANISMS IN PSYCHIATRIC AND BEHAVIORAL PHENOTYPES AMONG HUMANS. FINDINGS REVEALED SIGNIFICANT EPIGENETIC EFFECTS IN AN ASSORTMENT OF GENES THAT ARE IMPLICATED IN THE ETIOLOGY OF DEPRESSION, SUICIDALITY, CALLOUS-UNEMOTIONAL TRAITS, AND CHRONIC AND INTERGENERATIONAL AGGRESSIVE BEHAVIOR. SEVERAL POLYMORPHISMS THAT MEDIATE THE HPA AXIS, NEUROTRANSMISSION, IMMUNE RESPONSE, BRAIN DEVELOPMENT, SEROTONIN SYNTHESIS, AND OTHER PROCESSES WERE FOUND. ALTHOUGH PRESCRIPTIVE KNOWLEDGE BASED ON EPIGENETIC FINDINGS TO DATE IS PREMATURE, EPIGENETICS IS A NEW AND EXCITING SCIENTIFIC FRONTIER NOT TOO DIFFERENT IN SPIRIT FROM LAMARCK'S OBSERVATIONS CENTURIES AGO. 2015