1 4672 118 NEW INSIGHTS INTO THE MECHANISMS OF THE KETOGENIC DIET. PURPOSE OF REVIEW: HIGH-FAT, LOW-CARBOHYDRATE KETOGENIC DIETS HAVE BEEN USED FOR ALMOST A CENTURY FOR THE TREATMENT OF EPILEPSY. USED TRADITIONALLY FOR THE TREATMENT OF REFRACTORY PEDIATRIC EPILEPSIES, IN RECENT YEARS THE USE OF KETOGENIC DIETS HAS EXPERIENCED A REVIVAL TO INCLUDE THE TREATMENT OF ADULTHOOD EPILEPSIES AS WELL AS CONDITIONS RANGING FROM AUTISM TO CHRONIC PAIN AND CANCER. DESPITE THE ABILITY OF KETOGENIC DIET THERAPY TO SUPPRESS SEIZURES REFRACTORY TO ANTIEPILEPTIC DRUGS AND REPORTS OF LASTING SEIZURE FREEDOM, THE UNDERLYING MECHANISMS ARE POORLY UNDERSTOOD. THIS REVIEW EXPLORES NEW INSIGHTS INTO MECHANISMS MOBILIZED BY KETOGENIC DIET THERAPIES. RECENT FINDINGS: KETOGENIC DIETS ACT THROUGH A COMBINATION OF MECHANISMS, WHICH ARE LINKED TO THE EFFECTS OF KETONES AND GLUCOSE RESTRICTION, AND TO INTERACTIONS WITH RECEPTORS, CHANNELS, AND METABOLIC ENZYMES. DECANOIC ACID, A COMPONENT OF MEDIUM-CHAIN TRICLYCERIDES, CONTRIBUTES TO SEIZURE CONTROL THROUGH DIRECT ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID (AMPA) RECEPTOR INHIBITION, WHEREAS DRUGS TARGETING LACTATE DEHYDROGENASE REDUCE SEIZURES THROUGH INHIBITION OF A METABOLIC PATHWAY. KETOGENIC DIET THERAPY ALSO AFFECTS DNA METHYLATION, A NOVEL EPIGENETIC MECHANISM OF THE DIET. SUMMARY: KETOGENIC DIET THERAPY COMBINES SEVERAL BENEFICIAL MECHANISMS THAT PROVIDE BROAD BENEFITS FOR THE TREATMENT OF EPILEPSY WITH THE POTENTIAL TO NOT ONLY SUPPRESS SEIZURES BUT ALSO TO MODIFY THE COURSE OF THE EPILEPSY. 2017 2 6283 31 THE POTENTIAL OF A KETOGENIC DIET TO MINIMIZE EFFECTS OF THE METABOLIC FAULT IN GLYCOGEN STORAGE DISEASE V AND VII. PURPOSE OF REVIEW: TO EXPLORE THE POTENTIAL OF A LOW CARBOHYDRATE KETOGENIC DIET (LCKD) TO COUNTER PHYSICAL ACTIVITY INTOLERANCE, PAIN AND MUSCLE DAMAGE FOR GLYCOGEN STORAGE DISEASE (GSD) V AND VII, AND HIGHLIGHT THE REALISTIC POSSIBILITY THAT NUTRITION COULD BE KEY. RECENT FINDINGS: CARBOHYDRATE (CHO) INGESTION DURING PHYSICAL ACTIVITY IN GSDV AND A LCKD FOR GSDVII IS COMMON. FOR THE LATTER, A LONG-TERM STUDY DEMONSTRATED IMPROVEMENT IN PHYSIOLOGICAL MARKERS WHILE ON A LCKD. THIS INCLUDED IMPROVEMENT IN AEROBIC POWER AND ACTIVITY TOLERANCE. IN GSDV, PRELIMINARY RESEARCH ON A LCKD SUGGEST A DIET OF 75% FAT, 15% PROTEIN, 10% CHO, IS BEST FOR IMPROVED FUNCTION AND COMPLIANCE. KETONES PROVIDE IMMEDIATE FUEL FOR ACUTE PHYSICAL ACTIVITY, AND HAVE AN EPIGENETIC ROLE, IMPROVING KETONE AND LIPID USE. EVIDENCE FROM ELITE ATHLETES FOUND A LCKD CAN INCREASE FAT OXIDATION AND IS OPTIMAL AT 70% VO2MAX. THIS SUGGESTS THE NEED TO ALSO IMPROVE CONDITIONING VIA EXERCISE TO MAXIMIZE THE BENEFIT OF A LCKD. SUMMARY: A HIGH CHO DIET IN GSDV AND VII COMES WITH A RESTRICTED PHYSICAL ACTIVITY CAPACITY ALONGSIDE SIGNIFICANT PAIN, MUSCLE DAMAGE AND RISK OF RENAL FAILURE. MOUNTING EVIDENCE SUGGESTS A LCKD IS EFFICACIOUS FOR BOTH DISORDERS PROVIDING AN IMMEDIATE FUEL SOURCE WHICH MAY NEGATE THE NEED FOR A 'WARM-UP' PRIOR TO EVERY ACTIVITY AND RESTORE 'NORMAL' FUNCTION. 2020 3 3882 29 KETONE BODIES AS METABOLITES AND SIGNALLING MOLECULES AT THE CROSSROAD BETWEEN INFLAMMATION AND EPIGENETIC CONTROL OF CARDIOMETABOLIC DISORDERS. FOR MANY YEARS, IT HAS BEEN CLEAR THAT A WESTERN DIET RICH IN SATURATED FATS AND SUGARS PROMOTES AN INFLAMMATORY ENVIRONMENT PREDISPOSING A PERSON TO CHRONIC CARDIOMETABOLIC DISEASES. IN PARALLEL, THE EMERGENCE OF KETOGENIC DIETS, DEPRIVED OF CARBOHYDRATES AND PROMOTING THE SYNTHESIS OF KETONE BODIES IMITATING THE METABOLIC EFFECTS OF FASTING, HAS BEEN SHOWN TO PROVIDE A POSSIBLE NUTRITIONAL SOLUTION TO ALLEVIATING DISEASES TRIGGERED BY AN INFLAMMATORY ENVIRONMENT. THE MAIN KETONE BODY, BETA-HYDROXYBUTYRATE (BHB), ACTS AS AN ALTERNATIVE FUEL, AND ALSO AS A SUBSTRATE FOR A NOVEL HISTONE POST-TRANSLATIONAL MODIFICATION, BETA-HYDROXYBUTYRYLATION. BETA-HYDROXYBUTYRYLATION INFLUENCES THE STATE OF CHROMATIN ARCHITECTURE AND PROMOTES THE TRANSCRIPTION OF MULTIPLE GENES. BHB HAS ALSO BEEN SHOWN TO MODULATE INFLAMMATION IN CHRONIC DISEASES. IN THIS REVIEW, WE DISCUSS, IN THE PATHOLOGICAL CONTEXT OF CARDIOVASCULAR RISKS, THE CURRENT UNDERSTANDING OF HOW KETONE BODIES, OR A KETOGENIC DIET, ARE ABLE TO MODULATE, TRIGGER, OR INHIBIT INFLAMMATION AND HOW THE EPIGENOME AND CHROMATIN REMODELING MAY BE A KEY CONTRIBUTOR. 2022 4 128 31 A UNIFYING MECHANISM OF KETOGENIC DIET ACTION: THE MULTIPLE ROLES OF NICOTINAMIDE ADENINE DINUCLEOTIDE. THE ABILITY OF A KETOGENIC DIET TO TREAT SEIZURES AND RENDER A NEURONAL NETWORK MORE RESISTANT TO STRONG ELECTRICAL ACTIVITY HAS BEEN OBSERVED FOR A CENTURY IN CLINICS AND FOR DECADES IN RESEARCH LABORATORIES. ALONGSIDE ONGOING EFFORTS TO UNDERSTAND HOW THIS THERAPY WORKS TO STOP SEIZURES, METABOLIC HEALTH IS INCREASINGLY APPRECIATED AS CRITICAL BUFFER TO RESISTING AND RECOVERING FROM ACUTE AND CHRONIC DISEASE. ACCORDINGLY, LINKS BETWEEN METABOLISM AND HEALTH, AND THE BROADER EMERGING IMPACT OF THE KETOGENIC DIET IN IMPROVING DIVERSE METABOLIC, IMMUNOLOGICAL AND NEUROLOGICAL CONDITIONS, HAVE SERVED TO INTENSIFY THE SEARCH FOR ITS KEY AND/OR COMMON MECHANISMS. HERE WE REVIEW DIVERSE EVIDENCE FOR INCREASED LEVELS OF NAD(+), AND THUS AN ALTERED RATIO OF NAD(+)/NADH, DURING METABOLIC THERAPY WITH A KETOGENIC DIET. WE PROPOSE THIS AS A POTENTIAL UNIFYING MECHANISM, AND HIGHLIGHT SOME OF THE EVIDENCE LINKING ALTERED NAD(+)/NADH WITH REDUCED SEIZURES AND WITH A RANGE OF SHORT AND LONG-TERM CHANGES ASSOCIATED WITH THE BENEFICIAL EFFECTS OF A KETOGENIC DIET. AN INCREASE IN NAD(+)/NADH IS CONSISTENT WITH MULTIPLE LINES OF EVIDENCE AND HYPOTHESES, AND THEREFORE WE SUGGEST THAT INCREASED NAD(+) MAY BE A COMMON MECHANISM UNDERLYING BENEFICIAL EFFECTS OF KETOGENIC DIET THERAPY. 2020 5 2616 30 EPIGENOME MODULATION INDUCED BY KETOGENIC DIETS. KETOGENIC DIETS (KD) ARE DIETARY STRATEGIES LOW IN CARBOHYDRATES, NORMAL IN PROTEIN, AND HIGH, NORMAL, OR REDUCED IN FAT WITH OR WITHOUT (VERY LOW-CALORIES KETOGENIC DIET, VLCKD) A REDUCED CALORIC INTAKE. KDS HAVE BEEN SHOWN TO BE USEFUL IN THE TREATMENT OF OBESITY, METABOLIC DISEASES AND RELATED DISORDERS, NEUROLOGICAL DISEASES, AND VARIOUS PATHOLOGICAL CONDITIONS SUCH AS CANCER, NONALCOHOLIC LIVER DISEASE, AND CHRONIC PAIN. SEVERAL STUDIES HAVE INVESTIGATED THE INTRACELLULAR METABOLIC PATHWAYS THAT CONTRIBUTE TO THE BENEFICIAL EFFECTS OF THESE DIETS. ALTHOUGH EPIGENETIC CHANGES ARE AMONG THE MOST IMPORTANT DETERMINANTS OF AN ORGANISM'S ABILITY TO ADAPT TO ENVIRONMENTAL CHANGES, DATA ON THE EPIGENETIC CHANGES ASSOCIATED WITH THESE DIETARY PATHWAYS ARE STILL LIMITED. THIS REVIEW PROVIDES AN OVERVIEW OF THE MAJOR EPIGENETIC CHANGES ASSOCIATED WITH KDS. 2022 6 6859 25 [NUTRITIONAL FACTORS ASSOCIATED WITH MIGRAINE]. MIGRAINE IS A CHRONIC, HIGHLY PREVALENT, MULTIDIMENSIONAL, AND COMPLEX DISORDER, INFLUENCED BY GENETIC AND ENVIRONMENTAL FACTORS, AMONG WHICH IS THE DIET. MEDICAL TREATMENTS ARE PARTIALLY EFFECTIVE, AND THAT MAKES NECESSARY TO COMPLEMENT THEM WITH OTHER THERAPEUTIC STRATEGIES. THE NUTRITION PLAYS A PREVALENT ROLE. WE WILL REVIEW DIETARY FACTORS THAT HAVE BEEN LINKED TO MIGRAINE AND THERAPEUTIC NUTRITIONAL GUIDELINES ABOUT IT: ELIMINATION, INTEGRAL, KETOGENIC, EPIGENETIC AND HYPOCALORIC DIETS, AS WELL AS DIETS THAT INTEREST FATTY ACIDS, SODIUM, VITAMINS, AND THE GUT-BRAIN AXIS. TO DATE, THE EVIDENCE OF THE EFFICACY OF NUTRITIONAL TREATMENTS FOR MIGRAINE IS NOT WIDESPREAD AND IT IS NECESSARY TO ADVISE OUR PATIENTS ABOUT PATTERNS CONSISTENT WITH NUTRITIONAL GENERAL RECOMMENDATIONS. 2022 7 5154 30 PRAKRITI-BASED MEDICINE: A STEP TOWARDS PERSONALIZED MEDICINE. THE CONCEPT OF PERSONALIZED MEDICINE HAS BEEN AROUND FOR AS LONG AS PEOPLE HAVE BEEN PRACTICING MEDICINE. FROM CHARAKA TO HIPPOCRATES, ALL HAVE PRACTICED THE PERSONALIZED APPROACH FOR TREATING A DISEASE. IN THE 21(ST) CENTURY, PERSONALIZED MEDICINE IS ALL ABOUT DNA. WHEREAS THE SINGLE NUCLEOTIDE POLYMORPHISM (SNP) AND EPIGENETIC FACTORS INFLUENCE DRUG RESPONSE AND FORM THE BASIS OF PERSONALIZED MEDICINE, THE TRIDOSHA THEORY FORMS THE BASIS OF PRAKRITI-BASED MEDICINE. IT IS WELL ESTABLISHED BY NOW THAT WESTERN ALLOPATHIC MEDICINE IS EXCELLENT IN HANDLING ACUTE MEDICAL CRISES, WHEREAS AYURVEDA HAS SUCCESSFULLY DEMONSTRATED AN ABILITY TO MANAGE CHRONIC DISORDERS THAT WESTERN MEDICINE HAS BEEN UNABLE TO CURE. WITH EFFECTIVE INTEGRATION OF 'OMICS' PRAKRITI-BASED MEDICINE CAN PLAY A VITAL ROLE IN THIS CHANGING SCENARIO OF GLOBAL HEALTH WISDOM AS AYURVEDA OFFERS ITS MODALITIES BY WAY OF AHARA (DIET), VIHARA (LIFESTYLE), AND AUSHADHI (MEDICATION), WHICH ARE THE THREE PILLARS OF PRAKRITI-BASED MEDICINE MAKING IT A HOLISTIC SCIENCE. PRAKRITI-BASED MEDICINE AND OTHER TRADITIONAL MEDICINE SYSTEMS HAVE THE POTENTIAL TO OFFER REMEDIES TO THE CHALLENGING HEALTH ISSUES LIKE ADVERSE DRUG REACTIONS, DRUG WITHDRAWALS, AND ECONOMIC DISPARITIES AMONG FEW. AN INTEGRATIVE GLOBAL APPROACH COULD DO WONDERS TO HEALTH SCIENCES BENEFITING A BROAD SPECTRUM OF PATIENTS. 2011 8 5500 25 REVISITING MIGRAINE: THE EVOLVING PATHOPHYSIOLOGY AND THE EXPANDING MANAGEMENT ARMAMENTARIUM. MIGRAINE AFFECTS ABOUT ONE BILLION PEOPLE WORLDWIDE YEARLY AND IS ONE OF THE MOST COMMON NEUROLOGIC ILLNESSES, WITH A HIGH PREVALENCE AND MORBIDITY, PARTICULARLY AMONG YOUNG ADULTS AND FEMALES. MIGRAINE IS ASSOCIATED WITH MANY COMORBIDITIES, INCLUDING STRESS, SLEEP DIFFICULTIES, AND SUICIDAL IDEATION. MIGRAINE, DESPITE ITS WIDESPREAD OCCURRENCE, IS UNDERDIAGNOSED AND UNDERTREATED. BECAUSE OF THE COMPLICATED AND PRIMARILY UNKNOWN MECHANISMS OF MIGRAINE FORMATION, SEVERAL SOCIAL AND BIOLOGICAL RISK FACTORS, SUCH AS HORMONE IMBALANCES, GENETIC AND EPIGENETIC IMPACTS, AND CARDIOVASCULAR, NEUROLOGICAL, AND AUTOIMMUNE ILLNESSES, HAVE BEEN PROPOSED. THROUGH THE MID-20TH CENTURY DIVERSION OF THE NOW-DEFUNCT VASCULAR THEORY, THE PATHOPHYSIOLOGY OF MIGRAINE HAS DEVELOPED FROM A HISTORICAL STUDY OF THE "HUMOURS" TO A DISTINCT ENTITY AS A NEUROLOGICAL DISORDER. THE RANGE OF THERAPEUTIC TARGETS HAS BROADENED SIGNIFICANTLY, INCREASING THE NUMBER OF SPECIALIZED CLINICAL TRIALS. UNDERSTANDING THE BIOLOGY OF MIGRAINE THROUGH CAREFUL RESEARCH HAS RESULTED IN THE IDENTIFICATION OF MAJOR THERAPEUTIC CLASSES: (I) TRIPTANS, SEROTONIN 5-HT1B/1D RECEPTOR AGONISTS, (II) GEPANTS, CALCITONIN GENE-RELATED PEPTIDE (CGRP) RECEPTOR ANTAGONISTS, (III) DITANS, 5-HT1F RECEPTOR AGONISTS, (IV) CGRP MONOCLONAL ANTIBODIES, AND (V) GLURANTS, MGLU5 MODULATORS, WITH FURTHER TARGETS BEING EXPLORED. THIS REVIEW PROVIDES A COMPREHENSIVE OVERVIEW OF THE MOST RECENT LITERATURE ON EPIDEMIOLOGY AND RISK FACTORS AND EXPOSES KNOWLEDGE GAPS. 2023 9 3881 33 KETOGENIC DIETS AND THE NERVOUS SYSTEM: A SCOPING REVIEW OF NEUROLOGICAL OUTCOMES FROM NUTRITIONAL KETOSIS IN ANIMAL STUDIES. OBJECTIVES: KETOGENIC DIETS HAVE REPORTED EFFICACY FOR NEUROLOGICAL DYSFUNCTIONS; HOWEVER, THERE ARE LIMITED PUBLISHED HUMAN CLINICAL TRIALS ELUCIDATING THE MECHANISMS BY WHICH NUTRITIONAL KETOSIS PRODUCES THERAPEUTIC EFFECTS. THE PURPOSE OF THIS PRESENT STUDY WAS TO INVESTIGATE ANIMAL MODELS THAT REPORT VARIATIONS IN NERVOUS SYSTEM FUNCTION BY CHANGING FROM A STANDARD ANIMAL DIET TO A KETOGENIC DIET, SYNTHESISE THESE INTO BROAD THEMES, AND COMPARE THESE WITH MECHANISMS REPORTED AS TARGETS IN PAIN NEUROSCIENCE TO INFORM HUMAN CHRONIC PAIN TRIALS. METHODS: AN ELECTRONIC SEARCH OF SEVEN DATABASES WAS CONDUCTED IN JULY 2020. TWO INDEPENDENT REVIEWERS SCREENED STUDIES FOR ELIGIBILITY, AND DESCRIPTIVE OUTCOMES RELATING TO NERVOUS SYSTEM FUNCTION WERE EXTRACTED FOR A THEMATIC ANALYSIS, THEN SYNTHESISED INTO BROAD THEMES. RESULTS: IN TOTAL, 170 STUDIES FROM EIGHTEEN DIFFERENT DISEASE MODELS WERE IDENTIFIED AND GROUPED INTO FOURTEEN BROAD THEMES: ALTERATIONS IN CELLULAR ENERGETICS AND METABOLISM, BIOCHEMICAL, CORTICAL EXCITABILITY, EPIGENETIC REGULATION, MITOCHONDRIAL FUNCTION, NEUROINFLAMMATION, NEUROPLASTICITY, NEUROPROTECTION, NEUROTRANSMITTER FUNCTION, NOCICEPTION, REDOX BALANCE, SIGNALLING PATHWAYS, SYNAPTIC TRANSMISSION AND VASCULAR SUPPLY. DISCUSSION: THE MECHANISMS PRESENTED CENTRED AROUND THE REDUCTION OF INFLAMMATION AND OXIDATIVE STRESS AS WELL AS A REDUCTION IN NERVOUS SYSTEM EXCITABILITY. GIVEN THE MULTIPLE POTENTIAL MECHANISMS PRESENTED, IT IS LIKELY THAT MANY OF THESE ARE INVOLVED SYNERGISTICALLY AND UNDERGO ADAPTIVE PROCESSES WITHIN THE HUMAN BODY, AND CONTROLLED ANIMAL MODELS THAT LIMIT THE INVESTIGATION TO A PARTICULAR PATHWAY IN ISOLATION MAY REACH DIFFERING CONCLUSIONS. ATTENTION IS REQUIRED WHEN TRANSLATING THIS INFORMATION TO HUMAN CHRONIC PAIN POPULATIONS OWING TO THE LIMITATIONS OUTLINED FROM THE ANIMAL RESEARCH. 2022 10 1 13 ON DECEMBER 5, 2017, THE NATIONAL ACADEMIES OF SCIENCES, ENGINEERING, AND MEDICINE HOSTED A PUBLIC WORKSHOP TITLED NUTRIGENOMICS AND THE FUTURE OF NUTRITION IN WASHINGTON, DC, TO REVIEW CURRENT KNOWLEDGE IN THE FIELD OF NUTRIGENOMICS AS IT RELATES TO NUTRITION. WORKSHOP PARTICIPANTS EXPLORED THE INFLUENCE OF GENETIC AND EPIGENETIC EXPRESSION ON NUTRITIONAL STATUS AND THE POTENTIAL IMPACT OF PERSONALIZED NUTRITION ON HEALTH MAINTENANCE AND CHRONIC DISEASE PREVENTION. THIS PUBLICATION SUMMARIZES THE PRESENTATIONS AND DISCUSSIONS FROM THE WORKSHOP. 2018 11 4418 28 MOLECULAR AND EPIGENETIC ASPECTS OF OPIOID RECEPTORS IN DRUG ADDICTION AND PAIN MANAGEMENT IN SPORT. OPIOIDS ARE SUBSTANCES DERIVED FROM OPIUM (NATURAL OPIOIDS). IN ITS RAW STATE, OPIUM IS A GUMMY LATEX EXTRACTED FROM PAPAVER SOMNIFERUM. THE USE OF OPIOIDS AND THEIR NEGATIVE HEALTH CONSEQUENCES AMONG PEOPLE WHO USE DRUGS HAVE BEEN STUDIED. TODAY, OPIOIDS ARE STILL THE MOST COMMONLY USED AND EFFECTIVE ANALGESIC TREATMENTS FOR SEVERE PAIN, BUT THEIR USE AND ABUSE CAUSES DETRIMENTAL SIDE EFFECTS FOR HEALTH, INCLUDING ADDICTION, THUS IMPACTING THE USER'S QUALITY OF LIFE AND CAUSING OVERDOSE. THE MESOCORTICOLIMBIC DOPAMINERGIC CIRCUITRY REPRESENTS THE BRAIN CIRCUIT MEDIATING BOTH NATURAL REWARDS AND THE REWARDING ASPECTS OF NEARLY ALL DRUGS OF ABUSE, INCLUDING OPIOIDS. HENCE, UNDERSTANDING HOW OPIOIDS AFFECT THE FUNCTION OF DOPAMINERGIC CIRCUITRY MAY BE USEFUL FOR BETTER KNOWLEDGE OF THE PROCESS AND TO DEVELOP EFFECTIVE THERAPEUTIC STRATEGIES IN ADDICTION. THE AIM OF THIS REVIEW WAS TO SUMMARIZE THE MAIN FEATURES OF OPIOIDS AND OPIOID RECEPTORS AND FOCUS ON THE MOLECULAR AND UPCOMING EPIGENETIC MECHANISMS LEADING TO OPIOID ADDICTION. SINCE SYNTHETIC OPIOIDS CAN BE EFFECTIVE FOR PAIN MANAGEMENT, THEIR ABILITY TO INDUCE ADDICTION IN ATHLETES, WITH THE RISK OF INCURRING DOPING, IS ALSO DISCUSSED. 2023 12 486 35 ASENAPINE TRANSDERMAL PATCH FOR THE MANAGEMENT OF SCHIZOPHRENIA. PURPOSE OF REVIEW: THIS IS A COMPREHENSIVE REVIEW OF THE LITERATURE REGARDING THE USE OF ASENAPINE FOR THE TREATMENT OF SCHIZOPHRENIA (SZ) IN ADULTS. IT COVERS AN INTRODUCTION, EPIDEMIOLOGY, RISK FACTORS, PATHOPHYSIOLOGY, AND CURRENT TREATMENT MODALITIES REGARDING SZ, PROVIDES A BACKGROUND ON THE MECHANISM OF ACTION OF ASENAPINE, AND THEN REVIEWS THE EXISTING EVIDENCE FOR USE OF ASENAPINE IN BOTH ITS SUBLINGUAL AND TRANSDERMAL FORMULATION IN THE TREATMENT OF SZ. RECENT FINDINGS: SZ IS A COMPLEX AND MULTIFACTORIAL MENTAL DISORDER WHICH IS THOUGHT TO COMBINE SEVERAL GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS CAUSING ABNORMALITIES IN THE DOPAMINERGIC SYSTEM. SYMPTOMS ARE CATEGORIZED IN DELUSIONS, HALLUCINATIONS, DISORGANIZATION, AND NEGATIVE PRESENTATIONS LIKE AFFECTIVE FLATTENING AND APATHY. CURRENT TREATMENT FOCUSES ON ANTIPSYCHOTIC MEDICATIONS BY MEANS OF ORAL ADMINISTRATION OR LONG-ACTING INJECTION. ASENAPINE IS A SECOND-GENERATION ANTIPSYCHOTIC WITH 5HT-2A ANTAGONIST AND 5HT-1A/1B PARTIAL AGONIST PROPERTIES, WHICH PROVIDES A FAVORABLE PROFILE IN TARGETING SCHIZOPHRENIC SYMPTOMS, WHILE REDUCING MOTOR SIDE EFFECTS AND IMPROVING MOOD AND COGNITION. ASENAPINE IN ITS SUBLINGUAL FORMULATION WAS FDA APPROVED FOR TREATMENT OF SZ AND BIPOLAR I DISORDER IN ADULTS IN AUGUST OF 2009 AND HAS BEEN PROVEN TO BE BOTH EFFECTIVE AND SAFE. TRANSDERMAL PATCH OF ASENAPINE (SECUADO) WAS FDA APPROVED IN OCTOBER OF 2019, THE FIRST AND ONLY FDA APPROVED PATCH FOR SZ IN ADULTS, WHICH OFFERS ANOTHER STRATEGY FOR TREATMENT TO IMPROVE COMPLIANCE AND EASE OF ADMINISTRATION. SUMMARY: SZ IS A CHRONIC AND DEBILITATING DISEASE WHICH IS STILL NOT WELL UNDERSTOOD AND COMES AT GREAT COST WITH REGARDS TO THE QUALITY OF LIFE FOR PATIENTS. MEDICATION SIDE-EFFECTS AND COMPLIANCE ARE ENORMOUS ISSUES WHICH TAKE A TOLL ON HEALTH CARE SYSTEMS IN INDUSTRIALIZED NATIONS AND KEEP PATIENTS FROM ACHIEVING STABILITY WITH THEIR DISEASE. TRANSDERMAL ASENAPINE IS A NEW FIRST-IN-CLASS DOSAGE FORM AND PROVIDES A NOVEL MODALITY OF ADMINISTRATION. IT HAS BEEN SHOWN TO BE EFFECTIVE IN REDUCING POSITIVE, AS WELL AS NEGATIVE SYMPTOMS, WHILE STILL MAINTAINING A FAVORABLE SIDE-EFFECT PROFILE. 2020 13 5809 26 STRAWBERRY AND HUMAN HEALTH: EFFECTS BEYOND ANTIOXIDANT ACTIVITY. THE USEFULNESS OF A DIET RICH IN VEGETABLES AND FRUITS ON HUMAN HEALTH HAS BEEN WIDELY RECOGNIZED: A HIGH INTAKE OF ANTIOXIDANT AND BIOACTIVE COMPOUNDS MAY IN FACT PLAY A CRUCIAL ROLE IN THE PREVENTION OF SEVERAL DISEASES, SUCH AS CANCER, CARDIOVASCULAR, NEURODEGENERATIVE, AND OTHER CHRONIC PATHOLOGIES. THE STRAWBERRY (FRAGARIA X ANANASSA DUCH.) POSSESSES A REMARKABLE NUTRITIONAL COMPOSITION IN TERMS OF MICRONUTRIENTS, SUCH AS MINERALS, VITAMIN C, AND FOLATES, AND NON-NUTRIENT ELEMENTS, SUCH AS PHENOLIC COMPOUNDS, THAT ARE ESSENTIAL FOR HUMAN HEALTH. ALTHOUGH STRAWBERRY PHENOLICS ARE KNOWN MAINLY FOR THEIR ANTI-INFLAMMATORY AND ANTIOXIDANT ACTIONS, RECENT STUDIES HAVE DEMONSTRATED THAT THEIR BIOLOGICAL ACTIVITIES ALSO SPREAD TO OTHER PATHWAYS INVOLVED IN CELLULAR METABOLISM AND CELLULAR SURVIVAL. THIS PAPER HAS THE MAIN OBJECTIVE OF REVIEWING CURRENT INFORMATION ABOUT THE POTENTIAL MECHANISMS INVOLVED IN THE EFFECTS ELICITED BY STRAWBERRY POLYPHENOLS ON HUMAN HEALTH, DEVOTING SPECIAL ATTENTION TO THE LATEST FINDINGS. 2014 14 2858 29 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 15 3598 14 IMPLICATIONS ON HYPNOTHERAPY: NEUROPLASTICITY, EPIGENETICS AND PAIN. WE PROVIDE A BRIEF REVIEW ABOUT THE SIGNIFICANCE OF HYPNOSIS WITH RESPECT TO APPLICATIONS AND PHYSIOLOGICAL PROCESSES IN HYPNOTHERAPY. OUR REVIEW CONCLUDES THAT HYPNOSIS IS A PROMISING METHOD TO MANAGE ACUTE AND CHRONIC PAIN. IN ADDITION, WE DISCUSS INDICATIONS POINTING TOWARD THE VIEW THAT HYPNOSIS CAN INDUCE CHANGES IN NEUROPLASTICITY POSSIBLY INVOLVING EPIGENETIC MECHANISMS. 2021 16 96 19 A PRIMER ON METABOLIC MEMORY: WHY EXISTING DIABESITY TREATMENTS FAIL. DESPITE MASSIVE GOVERNMENT AND PRIVATE SECTOR INVESTMENTS INTO PREVENTION OF CARDIOVASCULAR DISEASE, DIABETES MELLITUS AND OBESITY, EFFORTS HAVE LARGELY FAILED, AND THE BURDEN OF COST REMAINS IN THE TREATMENT OF DOWNSTREAM MORBIDITY AND MORTALITY, WITH OVERALL STAGNATING OUTCOMES. A NEW PARADIGM SHIFT IN THE APPROACH TO THESE PATIENTS MAY EXPLAIN WHY EXISTING TREATMENT STRATEGIES FAIL, AND OFFER NEW TREATMENT TARGETS. THIS REVIEW AIMS TO PROVIDE A CLINICIAN-CENTRED PRIMER ON METABOLIC MEMORY, DEFINED AS THE SUM OF IRREVERSIBLE GENETIC, EPIGENETIC, CELLULAR AND TISSUE-LEVEL ALTERATIONS THAT OCCUR WITH LONG-TIME EXPOSURE TO METABOLIC DERANGEMENTS. 2021 17 6577 28 TREATMENT STRATEGIES FOR COMPLEX BEHAVIORAL INSOMNIA IN CHILDREN WITH NEURODEVELOPMENTAL DISORDERS. PURPOSE OF REVIEW: THIS REVIEW DESCRIBES RECENT RESEARCH IN PEDIATRIC BEHAVIORAL INSOMNIAS IN NEURODEVELOPMENTAL DISORDERS AND THEIR TREATMENT. RECENT FINDINGS: INSOMNIA IN CHILDREN WITH AUTISM SPECTRUM DISORDER (ASD) AND OTHER NEURODEVELOPMENTAL DISORDERS (NDDS) IS TYPICALLY COMPLEX, CHRONIC, AND DIFFICULT TO ADEQUATELY CONTROL. ABNORMALITIES IN GENETIC AND/OR EPIGENETIC REGULATION OF SLEEP/WAKEFULNESS AND ITS TIMING PREDISPOSE PATIENTS WITH NDD TO INSOMNIA, ALTHOUGH POOR SLEEP HYGIENE, MALADAPTIVE ASSOCIATIONS, AND LIMIT-SETTING ARE LIKELY TO CONTRIBUTE. PARENTS ARE AGENTS FOR CHANGE IN PROBLEMATIC SLEEP BEHAVIORS IN PATIENTS WITH NDD. WE REVIEW THE BENEFITS OF BEHAVIORAL THERAPIES AND MELATONIN TO TREAT SLEEP PROBLEMS IN CHILDREN WITH NDD. PROBLEMATIC SLEEP IS SO PREVALENT IN SOME NEURODEVELOPMENTAL SYNDROMES (RETT, ANGELMAN, WILLIAMS, AND SMITH-MAGENIS) THAT IT IS PART OF THEIR DIAGNOSTIC CRITERIA. SUMMARY: CHILDREN AND ADOLESCENTS WITH NEUROLOGICAL DISORDERS FREQUENTLY HAVE COMPLEX SLEEP DISORDERS THAT REQUIRE TREATMENT. UNDERSTANDING THE BASIC PATHOLOGY AND TREATMENT STRATEGIES PROVIDES AN OPPORTUNITY TO IMPROVE WELL BEING AND QUALITY OF LIFE IN THOSE AFFECTED BY NDD AND THEIR FAMILIES. 2013 18 5516 21 RISE OF THE MUTANTS: REPORT FROM THE 19TH CONFERENCE OF THE EUROPEAN HAEMATOLOGY ASSOCIATION, MILAN, 12-15 JUNE 2014. AT THE 19TH CONFERENCE OF THE EUROPEAN HAEMATOLOGY ASSOCIATION IN MILAN, WE SAW THE TRUE AND DRAMATIC CHANGES BROUGHT ABOUT BY THE INTEGRATION OF EXTENSIVE GENOMIC INFORMATION IN CLINICAL PRACTICE, AND THE DILEMMAS THAT ACCOMPANY SUCH A RAPID INCREASE IN KNOWLEDGE. EACH DISEASE IS SLICED MORE AND MORE INTO SMALLER PIECES, EACH WITH ITS OWN BETTER-DETERMINED OUTCOME AND TREATMENT. WE ALSO OBSERVED THE RISE OF MUTANT-SPECIFIC EPIGENETIC AGENTS, WHICH BENEFIT FROM KNOWING THE UNDERLYING GENETIC ABNORMALITY TO SPECIFICALLY ASSIGN AN EPIGENETIC DRUG WHERE IT IS NEEDED. IN CONTRAST TO THE 'ONE MUTATION, ONE DRUG' APPROACH, OTHERS ARE PURSUING THE SEARCH FOR DRUGS TARGETING PATHWAYS FUNDAMENTAL FOR THE SURVIVAL OF ALL OR MOST CANCER CELLS, SOMETIMES LOOKING AT MORE 'EXOTIC' PATHWAYS LIKE NEDDYLATION OR NUCLEAR EXPORT. 2014 19 2498 41 EPIGENETICS AND EPILEPSY PREVENTION: THE THERAPEUTIC POTENTIAL OF ADENOSINE AND METABOLIC THERAPIES. PREVENTION OF EPILEPSY AND ITS PROGRESSION REMAINS THE MOST URGENT NEED FOR EPILEPSY RESEARCH AND THERAPY DEVELOPMENT. NOVEL CONCEPTUAL ADVANCES ARE REQUIRED TO MEANINGFULLY ADDRESS THIS FUNDAMENTAL CHALLENGE. MALADAPTIVE EPIGENETIC CHANGES, WHICH INCLUDE METHYLATION OF DNA AND ACETYLATION OF HISTONES - AMONG OTHER MECHANISMS, ARE NOW WELL RECOGNIZED TO PLAY A FUNCTIONAL ROLE IN THE DEVELOPMENT OF EPILEPSY AND ITS PROGRESSION. THE METHYLATION HYPOTHESIS OF EPILEPTOGENESIS SUGGESTS THAT CHANGES IN DNA METHYLATION ARE IMPLICATED IN THE PROGRESSION OF THE DISEASE. IN THIS CONTEXT, GLOBAL DNA HYPERMETHYLATION IS PARTICULARLY ASSOCIATED WITH CHRONIC EPILEPSY. LIKEWISE, ACETYLATION CHANGES OF HISTONES HAVE BEEN LINKED TO EPILEPSY DEVELOPMENT. CLINICAL AS WELL AS EXPERIMENTAL EVIDENCE DEMONSTRATE THAT EPILEPSY AND ITS PROGRESSION CAN BE PREVENTED BY METABOLIC AND BIOCHEMICAL MANIPULATIONS THAT TARGET PREVIOUSLY UNRECOGNIZED EPIGENETIC FUNCTIONS CONTRIBUTING TO EPILEPSY DEVELOPMENT AND MAINTENANCE OF THE EPILEPTIC STATE. THIS REVIEW WILL DISCUSS EPIGENETIC MECHANISMS IMPLICATED IN EPILEPSY DEVELOPMENT AS WELL AS METABOLIC AND BIOCHEMICAL INTERACTIONS THOUGHT TO DRIVE EPILEPTOGENESIS. THEREFORE, METABOLIC AND BIOCHEMICAL MECHANISMS ARE IDENTIFIED AS NOVEL TARGETS FOR EPILEPSY PREVENTION. WE WILL SPECIFICALLY DISCUSS ADENOSINE BIOCHEMISTRY AS A NOVEL THERAPEUTIC STRATEGY TO RECONSTRUCT THE DNA METHYLOME AS ANTIEPILEPTOGENIC STRATEGY AS WELL AS METABOLIC MEDIATORS, SUCH AS BETA-HYDROXYBUTYRATE, WHICH AFFECT HISTONE ACETYLATION. FINALLY, METABOLIC DIETARY INTERVENTIONS (SUCH AS THE KETOGENIC DIET) WHICH HAVE THE UNIQUE POTENTIAL TO PREVENT EPILEPTOGENESIS THROUGH RECENTLY IDENTIFIED EPIGENETIC MECHANISMS WILL BE REVIEWED. THIS ARTICLE IS PART OF THE SPECIAL ISSUE ENTITLED 'NEW EPILEPSY THERAPIES FOR THE 21ST CENTURY - FROM ANTISEIZURE DRUGS TO PREVENTION, MODIFICATION AND CURE OF EPILEPSY'. 2020 20 4808 24 OBESITY MANAGEMENT: AT THE FOREFRONT AGAINST DISEASE STIGMA AND THERAPEUTIC INERTIA. OBESITY IS A COMPLEX CHRONIC RELAPSING DISEASE, RESULTING FROM THE INTERACTION BETWEEN MULTIPLE ENVIRONMENTAL, GENETIC AND EPIGENETIC CAUSES, AND SUPPORTED BY CHANGES IN THE NEUROENDOCRINE MECHANISMS REGULATING ENERGY BALANCE AND BODY WEIGHT. ADIPOSE TISSUE DYSFUNCTION CONTRIBUTES TO OBESITY-RELATED COMPLICATIONS. HOWEVER, THE PREVALENT NARRATIVE ABOUT THE CAUSES AND MECHANISMS OF OBESITY REMAINS A MUCH MORE SIMPLISTIC ONE, BASED ON THE FALSE ASSUMPTION THAT INDIVIDUALS CAN FULLY CONTROL THEIR BODY WEIGHT THROUGH APPROPRIATE BEHAVIOURAL CHOICES. ACCORDING TO THIS NARRATIVE, OBESITY IS SIMPLY REVERSIBLE "PERSUADING" THE PATIENT TO FOLLOW HEALTHIER AND MORE VIRTUOUS INDIVIDUAL BEHAVIOURS (MORAL JUDGEMENT). THIS PERSISTENT NARRATIVE FORMS THE DEEP ROOT OF THE STIGMATISATION OF PEOPLE WITH OBESITY AT THE INDIVIDUAL LEVEL AND CREATES A CLEAR DISCREPANCY ON HOW OBESITY PREVENTION AND CURE ARE DESIGNED IN COMPARISON WITH THE CASE OF OTHER NON-COMMUNICABLE CHRONIC DISEASES (CLINICAL STIGMA). THE PROMOTION OF SYSTEMIC PREVENTIVE MEASURES AGAINST OBESITY IS NOT SUPPORTED AT A POLITICAL AND SOCIAL LEVEL BY THE PERSISTENCE OF A NARRATIVE OF OBESITY AS THE SIMPLE CONSEQUENCE OF INDIVIDUAL FAILURES AND LACK OF WILLPOWER. THE SIMPLISTIC NARRATIVE OF OBESITY AS A SELF-IMPOSED CONDITION WITH AN EASY WAY-OUT ("EAT LESS AND MOVE MORE") CREATES A CLEAR DISCREPANCY ON HOW OBESITY IS MANAGED BY HEALTH CARE SYSTEMS IN COMPARISON WITH OTHER NCDS. THE OVER-ESTIMATION OF THE EFFICACY OF THERAPEUTIC INTERVENTION SOLELY BASED ON PATIENTS EDUCATION AND LIFESTYLE MODIFICATION IS RESPONSIBLE OF THERAPEUTIC INERTIA IN HEALTH CARE PROFESSIONALS AND IN CLINICAL GUIDELINES, LIMITING OR DELAYING THE ADOPTION OF MORE EFFECTIVE THERAPEUTIC STRATEGIES, LIKE ANTI-OBESITY MEDICATIONS AND BARIATRIC SURGERY. IN CONCLUSION, THE PERSISTENCE OF A NARRATIVE DESCRIBING OBESITY AS A SELF-INDUCED EASILY REVERSIBLE CONDITION HAS PROFOUND CONSEQUENCES ON HOW OBESITY PREVENTION AND MANAGEMENT ARE BUILD, INCLUDING THE DESIGN AND IMPLEMENTATION OF OBESITY MANAGEMENT GUIDELINES AND A TENDENCY TO THERAPEUTIC INERTIA.LEVEL OF EVIDENCE: NO LEVEL OF EVIDENCE. 2022