ALGINATE DISPLAYS EXCELLENT BIOCOMPATIBILITY AND BIODEGRADABILITY AND HAS MANY DIFFERENT APPLICATIONS IN BIOMEDICINE AND THE FOOD INDUSTRY. ALGINATE-BASED BIOMATERIALS CAN BE USED IN REGENERATIVE MEDICINE AS A DRUG DELIVERY SYSTEM AND CELL CARRIER. IN FOOD APPLICATIONS, IT IS A POPULAR INGREDIENT, FOOD ADDITIVE, AND CARRIER OF ESSENTIAL COMPONENTS IN ALGINATE GEL ENCAPSULATION. THE ANIONIC POLYSACCHARIDE CAN BE EASILY MODIFIED VIA CHEMICAL AND PHYSICAL REACTIONS TO OBTAIN THREE-DIMENSIONAL (3D) SCAFFOLDING DERIVATIVES SUCH AS HYDROGELS, MICROSPHERES, MICROCAPSULES, SPONGES, FOAMS, AND FIBERS. ALGINATE-DERIVED SUPPORTED MATRICES? BIODEGRADABILITY, BIOCOMPATIBILITY, MECHANICAL STRENGTH, AND EXCEPTIONAL CHELATING PROPERTIES MAKE THEM USEFUL FOR A BROAD RANGE OF APPLICATIONS. THIS CHAPTER FOCUSES ON RECENT ADVANCES IN THE USE OF ALGINATE AND ITS DERIVATIVES IN THE BIOMEDICAL AND FOOD INDUSTRIES, INCLUDING USES SUCH AS WOUND HEALING, CARTILAGE AND BONE REGENERATION, DRUG DELIVERY, FOOD ADDITIVES, AND, IN ENCAPSULATED FORM, CARRIERS OF MICRONUTRIENTS AND BIOACTIVE COMPONENTS.

ASTROCYTE REACTIVITY IS ASSOCIATED WITH POOR REPAIR CAPACITY AFTER INJURY TO THE BRAIN, WHERE CHEMICAL AND PHYSICAL CHANGES OCCUR IN THE DAMAGED ZONE. ASTROCYTE SURFACE PROTEINS, SUCH AS INTEGRINS, ARE UPREGULATED, AND THE RELEASE OF PRO-INFLAMMATORY MOLECULES AND EXTRACELLULAR MATRIX (ECM) PROTEINS UPON DAMAGE GENERATE A STIFFER MATRIX. INTEGRINS PLAY AN IMPORTANT ROLE IN TRIGGERING A REACTIVE PHENOTYPE IN ASTROCYTES, AND WE HAVE REPORTED THAT ? V ?3 INTEGRIN BINDS TO THE THY-1 (CD90) NEURONAL GLYCOPROTEIN, INCREASING ASTROCYTE CONTRACTILITY AND MOTILITY. ALTERNATIVELY, ? V ?3 INTEGRIN SENSES MECHANICAL FORCES GENERATED BY THE INCREASED ECM STIFFNESS. UNTIL NOW, THE ASSOCIATION BETWEEN THE ? V ?3 INTEGRIN MECHANORECEPTOR RESPONSE IN ASTROCYTES AND CHANGES IN THEIR REACTIVE PHENOTYPE IS UNCLEAR. TO STUDY THE RESPONSE TO COMBINED CHEMICAL AND MECHANICAL STRESS, ASTROCYTES WERE STIMULATED WITH THY-1-PROTEIN A-COATED MAGNETIC BEADS AND EXPOSED TO A MAGNETIC FIELD TO GENERATE MECHANICAL TENSION. WE EVALUATED THE EFFECT OF SUCH STIMULATION ON CELL ADHESION AND CONTRACTION. WE ALSO ASSESSED TRACTION FORCES AND THEIR EFFECT ON CELL MORPHOLOGY, AND INTEGRIN SURFACE EXPRESSION. MECHANICAL STRESS ACCELERATED THE RESPONSE OF ASTROCYTES TO THY-1 ENGAGEMENT OF INTEGRIN RECEPTORS, RESULTING IN CELL ADHESION AND CONTRACTION. ASTROCYTE CONTRACTION THEN EXERTED TRACTION FORCES ONTO THE ECM, INDUCING FASTER CELL CONTRACTILITY AND HIGHER TRACTION FORCES THAN THY-1 ALONE. THEREFORE, CELL-EXTRINSIC CHEMICAL AND MECHANICAL SIGNALS REGULATE IN AN OUTSIDE-IN MANNER, ASTROCYTE REACTIVITY BY INDUCING INTEGRIN UPREGULATION, LIGATION, AND SIGNALING EVENTS THAT PROMOTE CELL CONTRACTION. THESE CHANGES IN TURN GENERATE CELL-INTRINSIC SIGNALS THAT INCREASE TRACTION FORCES EXERTED ONTO THE ECM (INSIDE-OUT). THIS STUDY REVEALS ? V ?3 INTEGRIN MECHANORECEPTOR AS A NOVEL TARGET TO REGULATE THE HARMFUL EFFECTS OF REACTIVE ASTROCYTES IN NEURONAL HEALING.

OUR FINDINGS IDENTIFY A PREVIOUSLY UNIDENTIFIED ROLE FOR SCAFFOLDING PROTEIN EZRIN-RADIXIN-MOESIN-BINDING PHOSPHOPROTEIN 50 (EBP50; AKA NHERF1) IN THE ACTIVATION OF NADPH OXIDASES (NOX), A FAMILY OF PROFESSIONAL REACTIVE OXYGEN SPECIES (ROS) PRODUCING ENZYMES IMPLICATED IN NUMEROUS PATHOLOGIES. WE DEMONSTRATE THAT EBP50 IS CRITICAL FOR AGONIST-INDUCED PRODUCTION OF ROS SUPEROXIDE ANION (O2??), AND THAT IT DIRECTLY ASSOCIATES WITH THE NOX ORGANIZING SUBUNIT P47PHOX. EBP50 DELETION ABOLISHES ANGIOTENSIN II-INDUCED CELLULAR HYPERTROPHY AND RESISTANCE ARTERY VASOCONSTRICTION. GIVEN THE WIDE ARRAY OF EBP50 CELLULAR INTERACTIONS AND THE UBIQUITY OF NOX, THE CURRENT FINDINGS SUPPORT A BROADER, MORE COMPLEX ORCHESTRATION OF NOX REGULATION THAN IS CURRENTLY HYPOTHESIZED. THE FINDINGS COULD AUGMENT FUTURE STRATEGIES TARGETING THIS INTERACTION IN DISEASE INVOLVING ABERRANT ROS, TISSUE REMODELING, AND/OR SMOOTH MUSCLE CONSTRICTION.

MATERNAL THYROID ALTERATIONS HAVE BEEN WIDELY ASSOCIATED WITH THE RISK OF GESTATIONAL DIABETES MELLITUS (GDM). THIS STUDY AIMS TO 1) TEST THE FIRST AND THE SECOND TRIMESTER FULL MATERNAL THYROID PROFILE ON THE PREDICTION OF GDM, BOTH ALONE AND COMBINED WITH NON-THYROID DATA; AND 2) MAKE THAT PREDICTION INDEPENDENT OF THE DIAGNOSTIC CRITERIA, BY EVALUATING THE EFFECTIVENESS OF THE DIFFERENT MATERNAL VARIABLES ON THE PREDICTION OF ORAL GLUCOSE TOLERANCE TEST (OGTT) POST LOAD GLYCEMIA. PREGNANT WOMEN WERE RECRUITED IN CONCEPCIO ?N, CHILE. GDM DIAGNOSIS WAS PERFORMED AT 24?28 WEEKS OF PREGNANCY BY AN OGTT (N = 54 FOR NORMAL GLU- COSE TOLERANCE, N = 12 FOR GDM). 75 MATERNAL THYROID AND NON-THYROID PARAMETERS WERE RECORDED IN THE FIRST AND THE SECOND TRIMESTER OF PREGNANCY. VARIOUS COMBINATIONS OF VARIABLES WERE ASSESSED FOR GDM AND POST LOAD GLYCEMIA PREDICTION THROUGH DIFFERENT CLASSIFICATION AND REGRESSION MACHINE LEARNING TECHNIQUES. THE BEST PREDICTIVE MODELS WERE SIMPLIFIED BY VARIABLE SELECTION. EVERY MODEL WAS SUBJECTED TO LEAVE-ONE-OUT CROSS-VALIDATION. OUR RESULTS INDICATE THAT THYROID MARKERS ARE USEFUL FOR THE PREDICTION OF GDM AND POST LOAD GLYCEMIA, ESPECIALLY AT THE SECOND TRIMESTER OF PREGNANCY. THUS, THEY COULD BE USED AS AN ALTERNATIVE SCREENING TOOL FOR GDM, INDEPENDENTLY OF THE DIAGNOSTIC CRITERIA USED. THE FINAL CLASSIFICATION MODELS PREDICT GDM WITH CROSS-VALIDATION AREAS UNDER THE RECEIVER OPERATING CHARACTERISTIC CURVE OF 0.867 (P

OBJECTIVES: TO IDENTIFY FIRST TRIMESTER MATERNAL GYNECO-OBSTETRIC VARIABLES THAT MAY BE USEFUL FOR GESTATIONAL DIABETES MELLITUS (GDM) PREDICTION IN CHILEAN PREGNANT WOMEN. METHODS: PREGNANT WOMEN WITH ? 12 GESTATIONAL WEEKS AND WITHOUT PREGESTATIONAL DIABETES WERE RECRUITED IN CONCEPCION, CHILE. DURING THE FIRST TRIMESTER OF PREGNANCY, 19 GYNECO-OBSTETRIC VARIABLES WERE REGISTERED: MATERNAL AGE, HEIGHT, WEIGHT, BODY MASS INDEX, SYSTOLIC PRESSURE, DIASTOLIC PRESSURE, PRIOR GDM, POLYCYSTIC OVARIAN SYNDROME, DIO2 GENOTYPE, FTO GENOTYPE, GLYCEMIA, TSH, TOTAL T3, TOTAL T4, FREE T4, THYROGLOBULIN, THYROGLOBULIN ANTIBODY (TGAB), THYROID PEROXIDASE ANTIBODY (ANTI-TPO) AND TSH RECEPTOR ANTIBODY (TRAB). GDM DIAGNOSIS WAS PERFORMED AT 24-28 GESTATIONAL WEEKS, WITH POSTLOAD GLYCEMIA (75G, 2H) ? 140 MG/DL. OUT OF 39 PREGNANT WOMEN, 6 WERE DIAGNOSED WITH GDM. DATA WERE ANALYZED BY UNIVARIATE AND MULTIVARIATE APPROACHES. FOR UNIVARIATE ANALYSIS, FISHERS EXACT, STUDENTS T AND MANN-WHITNEY TESTS WERE EMPLOYED; WHILE FOR MULTIVARIATE ANALYSIS, THE MACHINE LEARNING TECHNIQUE PRINCIPAL COMPONENT ANALYSIS (PCA) WAS APPLIED. RESULTS: ACCORDING TO THE UNIVARIATE ANALYSIS, THE ONLY FIRST TRIMESTER VARIABLES THAT ENABLE TO DIFFERENTIATE THE GDM GROUP FROM THE NON-GDM ONE ARE SYSTOLIC PRESSURE (P=0.0454) AND PRIOR GDM (P=0.0002). IN CONTRAST, THE MULTIVARIATE ANALYSIS SHOWS THAT GDM PREGNANT WOMEN CAN BE DISTINGUISHED FROM THE NON-GDM ONES BY THE SIXTH PRINCIPAL COMPONENT (PC6, 7% VARIANCE), WHICH IS A LINEAL COMBINATION OF VARIABLES WHERE THE MAIN CONTRIBUTORS ARE: FTO GENOTYPE, PRIOR GDM, TOTAL T3, DIASTOLIC PRESSURE, ANTI-TPO AND TRAB. CONCLUSION: THE FIRST TRIMESTER MATERNAL VARIABLES SYSTOLIC PRESSURE, PRIOR GDM, FTO GENOTYPE, TOTAL T3, DIASTOLIC PRESSURE, ANTI-TPO AND TRAB, ARE RELEVANT TO DISCRIMINATE BETWEEN GDM AND NON-GDM PREGNANT WOMEN. THEREFORE, THEY MAY BE HELPFUL FOR GDM PREDICTION.

INTRODUCTION: MACHINE LEARNING (ML) CORRESPONDS TO A WIDE VARIETY OF METHODS THAT USE MATHEMATICS, STATISTICS AND COMPUTATIONAL SCIENCE TO LEARN FROM MULTIPLE VARIABLES SIMULTANEOUSLY. BY MEANS OF PATTERN RECOGNITION, ML METHODS ARE ABLE TO FIND HIDDEN CORRELATIONS AND ACCOMPLISH ACCURATE PREDICTIONS REGARDING DIFFERENT CONDITIONS. ML HAS BEEN SUCCESSFULLY USED TO SOLVE VARIED PROBLEMS IN DIFFERENT AREAS OF SCIENCE, SUCH AS PSYCHOLOGY, ECONOMICS, BIOLOGY AND CHEMISTRY. THEREFORE, WE WONDERED HOW FAR IT HAS PENETRATED INTO THE FIELD OF OBSTETRICS AND GYNECOLOGY. AIM: TO DESCRIBE THE STATE OF ART REGARDING THE USE OF ML IN THE CONTEXT OF PREGNANCY DISEASES AND COMPLICATIONS. METHODOLOGY: PUBLICATIONS WERE SEARCHED IN PUBMED, WEB OF SCIENCE AND GOOGLE SCHOLAR. SEVEN SUBJECTS OF INTEREST WERE CONSIDERED: GESTATIONAL DIABETES MELLITUS, PREECLAMPSIA, PERINATAL DEATH, SPONTANEOUS ABORTION, PRETERM BIRTH, CESAREAN SECTION, AND FETAL MALFORMATIONS. CURRENT STATE: ML HAS BEEN WIDELY APPLIED IN ALL THE INCLUDED SUBJECTS. ITS USES ARE VARIED, THE MOST COMMON BEING THE PREDICTION OF PERINATAL DISORDERS. OTHER ML APPLICATIONS INCLUDE (BUT ARE NOT RESTRICTED TO) BIOMARKER DISCOVERY, RISK ESTIMATION, CORRELATION ASSESSMENT, PHARMACOLOGICAL TREATMENT PREDICTION, DRUG SCREENING, DATA ACQUISITION AND DATA EXTRACTION. MOST OF THE REVIEWED ARTICLES WERE PUBLISHED IN THE LAST FIVE YEARS. THE MOST EMPLOYED ML METHODS IN THE FIELD ARE NON-LINEAR. EXCEPT FOR LOGISTIC REGRESSION, LINEAR METHODS ARE RARELY USED. FUTURE CHALLENGES: TO IMPROVE DATA RECORDING, STORAGE AND UPDATE IN MEDICAL AND RESEARCH SETTINGS FROM DIFFERENT REALITIES. TO DEVELOP MORE ACCURATE AND UNDERSTANDABLE ML MODELS USING DATA FROM CUTTING-EDGE INSTRUMENTS. TO CARRY OUT VALIDATION AND IMPACT ANALYSIS STUDIES OF CURRENTLY EXISTING HIGH-ACCURACY ML MODELS. CONCLUSION: THE USE OF ML IN PREGNANCY DISEASES AND COMPLICATIONS IS QUITE RECENT, AND HAS INCREASED OVER THE LAST FEW YEARS. THE APPLICATIONS ARE VARIED AND POINT N

GESTATIONAL DIABETES MELLITUS (GDM) IS A HYPERGLYCEMIA STATE THAT IMPAIRS MATERNAL AND OFFSPRING HEALTH, SHORT AND LONG-TERM. IT IS USUALLY DIAGNOSED AT 24?28 WEEKS OF PREGNANCY (WP), BUT AT THAT TIME THE FETAL PHENOTYPE IS ALREADY ALTERED. MACHINE LEARNING (ML)-BASED MODELS HAVE EMERGED AS AN AUSPICIOUS ALTERNATIVE TO PREDICT THIS PATHOLOGY EARLIER, HOWEVER, THEY MUST BE VALIDATED IN DIFFERENT POPULATIONS BEFORE THEIR IMPLEMENTATION IN ROUTINE CLINICAL PRACTICE. THIS REVIEW AIMS TO GIVE AN OVERVIEW OF THE ML-BASED MODELS THAT HAVE BEEN PROPOSED TO PREDICT GDM BEFORE 24?28 WP, WITH SPECIAL EMPHASIS ON THEIR CURRENT VALIDATION STATE AND PREDICTIVE PER- FORMANCE. ARTICLES WERE SEARCHED IN PUBMED. MANUSCRIPTS WRITTEN IN ENGLISH AND PUBLISHED BEFORE JANUARY 1, 2022, WERE CONSIDERED. 109 ORIGINAL RESEARCH STUDIES WERE SELECTED, AND CATEGORIZED ACCORDING TO THE TYPE OF VARIABLES THAT THEIR MODELS INVOLVED: MEDICAL, I.E. CLINICAL AND/OR BIOCHEMICAL PARAMETERS; ALTERNATIVE, I.E. METABOLITES, PEPTIDES OR PROTEINS, MICRO-RIBONUCLEIC ACID MOLECULES, MICROBIOTA GENERA, OR OTHER VARIABLES THAT DID NOT FIT INTO THE FIRST CATEGORY; OR MIXED, I.E. BOTH MEDICAL AND ALTERNATIVE DATA. ONLY 8.3 % OF THE REVIEWED MODELS HAVE HAD VALIDATION IN INDEPENDENT STUDIES, WITH LOW OR MODERATE PERFORMANCE FOR GDM PREDICTION. IN CONTRAST, SEVERAL MODELS THAT LACK OF INDEPENDENT VALIDATION HAVE SHOWN A VERY HIGH PREDICTIVE POWER. THE EVALUATION OF THESE PROMISING MODELS IN FUTURE INDEPENDENT VALIDATION STUDIES WOULD ALLOW TO ASSESS THEIR PERFORMANCE ON DIFFERENT POPULATIONS, AND CONTINUE THEIR WAY TOWARDS CLINICAL IMPLEMENTATION. ONCE SETTLED, ML-BASED MODELS WOULD HELP TO PREDICT GDM EARLIER, INITIATE ITS TREATMENT TIMELY AND PREVENT ITS NEGATIVE CONSEQUENCES ON MATERNAL AND OFFSPRING HEALTH.

THERE IS EVIDENCE ABOUT A POSSIBLE RELATIONSHIP BETWEEN THYROID ABNORMALITIES AND GESTATIONAL DIABETES MELLITUS (GDM). HOWEVER, THERE IS STILL NO CONCLUSIVE DATA ON THIS DEPENDENCE, SINCE NO STRONG CORRELATION HAS BEEN PROVED. IN THIS WORK, WE USED MACHINE LEARNING TO DETERMINE WHETHER THERE IS A CORRELATION BETWEEN MATERNAL THYROID PROFILE IN FIRST AND SECOND TRIMESTER OF PREGNANCY AND GDM. USING PRINCIPAL COMPONENT ANALYSIS, IT WAS POSSIBLE TO FIND AN EVIDENT CORRELATION BETWEEN BOTH, WHICH COULD BE USED AS A COMPLEMENT FOR A MORE SENSITIVE GDM DIAGNOSIS.

OBJECTIVE: BLOOD VESSEL HEMODYNAMICS HAVE PROFOUND INFLUENCES ON FUNCTION AND STRUCTURE OF VASCULAR CELLS. ONE OF THE MAIN MECHANICAL FORCES INFLUENCING VASCULAR SMOOTH MUSCLE CELLS (VSMC) IS CYCLIC STRETCH (CS). INCREASED CS STIMULATES REACTIVE OXYGEN SPECIES (ROS) PRODUCTION IN VSMC, LEADING TO THEIR DEDIFFERENTIATION, YET THE MECHANISMS INVOLVED ARE POORLY UNDERSTOOD. THIS STUDY WAS DESIGNED TO TEST THE HYPOTHESIS THAT PATHOLOGICAL CS STIMULATES NADPH OXIDASE ISOFORM 1 (NOX1)-DERIVED ROS VIA MEF2B, LEADING TO VSMC DYSFUNCTION VIA A SWITCH FROM A CONTRACTILE TO A SYNTHETIC PHENOTYPE. APPROACH AND RESULTS: USING A NEWLY DEVELOPED ISOFORM-SPECIFIC NOX1 INHIBITOR AND GENE SILENCING TECHNOLOGY, WE DEMONSTRATE THAT A NOVEL PATHWAY, INCLUDING MEF2B-NOX1-ROS, IS UPREGULATED UNDER PATHOLOGICAL STRETCH CONDITIONS, AND THIS PATHWAY PROMOTES A VSMC PHENOTYPIC SWITCH FROM A CONTRACTILE TO A SYNTHETIC PHENOTYPE. WE OBSERVED THAT CS (10% AT 1 HZ) MIMICKING SYSTEMIC HYPERTENSION IN HUMANS INCREASED NOX1 MRNA, PROTEIN LEVELS, AND ENZYMATIC ACTIVITY IN A TIME-DEPENDENT MANNER, AND THIS UPREGULATION WAS MEDIATED BY MEF2B. FURTHERMORE, WE SHOW THAT STRETCH-INDUCED NOX1-DERIVED ROS UPREGULATED A SPECIFIC MARKER FOR SYNTHETIC PHENOTYPE (OSTEOPONTIN), WHEREAS IT DOWNREGULATED CLASSICAL MARKERS FOR CONTRACTILE PHENOTYPE (CALPONIN1 AND SMOOTHELIN B). IN ADDITION, OUR DATA DEMONSTRATED THAT STRETCH-INDUCED NOX1 ACTIVATION DECREASES ACTIN FIBER DENSITY AND AUGMENTS MATRIX METALLOPROTEINASE 9 ACTIVITY, VSMC MIGRATION, AND VECTORIAL ALIGNMENT. CONCLUSIONS: THESE RESULTS SUGGEST THAT CS INITIATES A SIGNAL THROUGH MEF2B THAT POTENTIATES NOX1-MEDIATED ROS PRODUCTION AND CAUSES VSMC TO SWITCH TO A SYNTHETIC PHENOTYPE. THE DATA ALSO CHARACTERIZE A NEW NOX1 INHIBITOR AS A POTENTIAL THERAPY FOR TREATMENT OF VASCULAR DYSFUNCTION IN HYPERTENSION.

ALTHOUGH REDOX PROCESSES CLOSELY INTERPLAY WITH MECHANORESPONSES TO CONTROL VASCULAR REMODELING, REDOX PATHWAYS COUPLING MECHANOSTIMULATION TO CELLULAR CYTOSKELETAL ORGANIZATION REMAIN UNCLEAR. THE PERI/EPICELLULAR POOL OF PROTEIN DISULFIDE ISOMERASE-A1 (PECPDIA1) SUPPORTS POSTINJURY VESSEL REMODELING. USING DISTINCT MODELS, WE INVESTIGATED WHETHER PECPDIA1 COULD WORK AS A REDOX-DEPENDENT ORGANIZER OF CYTOSKELETAL MECHANORESPONSES. IN VASCULAR SMOOTH MUSCLE CELLS (VSMCS), PECPDIA1 IMMUNONEUTRALIZATION IMPAIRED STRESS FIBER ASSEMBLY IN RESPONSE TO EQUIBIAXIAL STRETCH AND, UNDER UNIAXIAL STRETCH, SIGNIFICANTLY PERTURBED CELL REPOSITIONING PERPENDICULARLY TO STRETCH ORIENTATION. DURING CYCLIC STRETCH, PECPDIA1 SUPPORTED THIOL OXIDATION OF THE KNOWN MECHANOSENSOR ?1-INTEGRIN AND PROMOTED POLARIZED COMPARTMENTALIZATION OF SULFENYLATED PROTEINS. USING TRACTION FORCE MICROSCOPY, WE SHOWED THAT PECPDIA1 ORGANIZES INTRACELLULAR FORCE DISTRIBUTION. THE NET CONTRACTILE MOMENT RATIO OF PLATELET-DERIVED GROWTH FACTOR-EXPOSED TO BASAL VSMCS DECREASED FROM 0.90 ± 0.09 (IGG-EXPOSED CONTROLS) TO 0.70 ± 0.08 AFTER PECPDI NEUTRALIZATION ( P < 0.05), TOGETHER WITH AN ENHANCED COEFFICIENT OF VARIATION FOR DISTRIBUTION OF FORCE MODULES, SUGGESTING INCREASED NOISE. MOREOVER, IN A SINGLE CELL MODEL, PECPDIA1 NEUTRALIZATION IMPAIRED MIGRATION PERSISTENCE WITHOUT AFFECTING TOTAL DISTANCE OR VELOCITY, WHEREAS SIRNA-MEDIATED TOTAL PDIA1 SILENCING DISABLED ALL SUCH VARIABLES OF VSMC MIGRATION. NEITHER EXPRESSION NOR TOTAL ACTIVITY OF THE MASTER MECHANOTRANSMITTER/REGULATOR RHOA WAS AFFECTED BY PECPDIA1 NEUTRALIZATION. HOWEVER, CYCLIC STRETCH-INDUCED FOCAL DISTRIBUTION OF MEMBRANE-BOUND RHOA WAS DISRUPTED BY PECPDI INHIBITION, WHICH PROMOTED A NONPOLARIZED PATTERN OF RHOA/CAVEOLIN-3 CLUSTER COLOCALIZATION. ACCORDINGLY, FRET BIOSENSORS SHOWED THAT PECPDIA1 SUPPORTS LOCALIZED RHOA ACTIVITY AT CELL PROTRUSIONS VERSUS PERINUCLEAR REGIONS. THUS, PECPDI ACTS AS A THIOL REDOX-DEPENDENT ORGANIZER AND NO

THIS STUDY DETERMINED LEVELS OF PHYSICAL ACTIVITY IN STUDENTS BY COMPARING THEM BASED ON GENDER, FACULTY, AND MAJOR AMONG UNIVERSITY STUDENTS DURING THE COVID-19 PANDEMIC. THE RESEARCH FOLLOWED A QUANTITATIVE APPROACH WITH A DESCRIPTIVE-COMPARATIVE DESIGN. THE STUDY WAS CONDUCTED ONCE PER STUDENT, WITH THE PARTICIPATION OF 582 STUDENTS OF BOTH GENDERS. THE INTERNATIONAL PHYSICAL ACTIVITY QUESTIONNAIRE (IPAQ) WAS ADMINISTERED TO THE STUDENTS USING GOOGLE FORMS, DISTRIBUTED THROUGH THEIR INSTITUTIONAL EMAILS. THE COLLECTED DATA WERE ANALYZED USING THE STATISTICAL SOFTWARE SPSS V.22.0. THE INDEPENDENT SAMPLES T-TEST WAS EMPLOYED TO COMPARE THE ENERGY EXPENDITURE BETWEEN MALES AND FEMALES, ALONG WITH COHEN'S D STATISTIC TO ASSESS THE EFFECT SIZE. PRIOR TO THESE ANALYSES, THE KOLMOGOROV-SMIRNOV NORMALITY TEST AND LEVENE'S TEST WERE CONDUCTED. RESULTS WERE CONSIDERED SIGNIFICANT WHEN THE P-VALUE WAS

OBJECTIVE: TO COMPARE THE PERFORMANCE OF NEAR-INFRARED (NIR) SPECTRA AND MATERNAL DATA BASED-MACHINE LEARNING (ML) MODELS FOR GESTATIONAL DIABETES MELLITUS (GDM) PREDICTION IN CHILEAN PREGNANT WOMEN. METHODOLOGY: PREGNANT WOMEN WITH ? 12 GESTATIONAL WEEKS AND WITHOUT PREGESTATIONAL DIABETES WERE RECRUITED IN CONCEPCION, CHILE. GDM DIAGNOSIS WAS PERFORMED AT 24-28 GESTATIONAL WEEKS, WITH FASTING GLYCEMIA 100-125 MG/DL OR POST-LOAD GLYCEMIA (75 G, 2 H) ? 140 MG/DL. DURING THE FIRST TRIMESTER OF PREGNANCY, SERA WERE COLLECTED, AND 63 CLINICAL AND BIOCHEMICAL MATERNAL VARIABLES WERE REGISTERED. FOR EACH SERUM SAMPLE, 5 NIR SPECTRA (RANGE 4000-10500 CM-1, RESOLUTION 4 CM-1) WERE RECORDED AND AVERAGED. FOR NIR SPECTRA, 80 DIFFERENT COMBINATIONS OF TRANSFORMATIONS (SAVITZKY-GOLAY SMOOTHING OR FIRST/SECOND DERIVATIVE WITH VARYING FILTER WIDTH, STANDARD NORMAL VARIATE SCATTERING CORRECTION, AUTOMATIC WEIGHTED LEAST SQUARES BASELINE CORRECTION, 2-NORM NORMALIZATION) WERE TESTED. NIR AND MATERNAL DATA WERE PREPROCESSED BY MEAN CENTERING AND AUTOSCALING, RESPECTIVELY. FOR GDM PREDICTION, THE CLASSIFICATION ML TECHNIQUE PARTIAL LEAST SQUARES-DISCRIMINANT ANALYSIS (PLS-DA) WAS EMPLOYED. EVERY MODEL WAS SUBJECTED TO LEAVE-ONE-OUT CROSS-VALIDATION. RESULTS: THE BEST NIR DATA-BASED MODEL WAS OBTAINED WITH SAVITZKY-GOLAY SMOOTHING (FILTER WIDTH 15, POLYNOMIAL ORDER 2) AND 2-NORM NORMALIZATION. IT ACHIEVED A CROSS-VALIDATION NON-ERROR RATE (CV-NER) OF 68% AND A CROSS-VALIDATION AREA UNDER THE RECEIVER OPERATING CHARACTERISTIC CURVE (CV-AUC) OF 0.669. THE MATERNAL DATA BASED-MODEL ACHIEVED A CV-NER OF 81% AND A CV-AUC OF 0.852. CONCLUSIONS: CLINICAL AND BIOCHEMICAL MATERNAL PARAMETERS ARE MORE USEFUL TO PREDICT GDM IN CHILEAN PREGNANT WOMEN THAN NIR SPECTRAL DATA.

FLUID SHEAR STRESS (FSS) IS ABLE TO GENERATE PHENOTYPIC CHANGES IN THE CELLS IN DIRECT CONTACT WITH THE STRAIN FORCE. IN ORDER TO DETECT AND TRANSDUCE FSS INTO INTRACELLULAR PATHWAYS, BIOLOGICAL SYSTEMS USE A SPECIFIC SET OF SENSORS, CALLED MECHANOSENSORS. THE PROCESS INVOLVES THE CONVERSION OF THE MECHANICAL FORCE INTO A CHEMICAL OR ELECTRICAL SIGNAL. PRIMARY CILIUM IS A NON-MOTILE ORGANELLE THAT EMANATES FROM THE CELL SURFACE OF MOST MAMMALIAN CELL TYPES THAT ACT AS A MECHANOSENSOR. INCREASING EVIDENCE SUGGESTS THAT PRIMARY CILIA ARE KEY COORDINATORS OF SIGNALING PATHWAYS IN TISSUE HOMEOSTASIS AND WHEN DEFECTIVE MAY CAUSE HUMAN DISEASES AND DEVELOPMENTAL DISORDERS. HERE, WE WILL DESCRIBE THE ENDOTHELIAL PRIMARY CILIUM AS A MECHANOTRANSDUCTORY ORGANELLE SENSING FSS. TO FULFILL THIS FUNCTION, PRIMARY CILIUM REQUIRES THE LOCALIZATION OF MECHANOPROTEINS, POLYCYSTIN-1 AND -2, IN THEIR MEMBRANE AND THE STRUCTURAL GENE PRODUCT, POLARIS. PHYSIOLOGICALLY, DEFLECTION OF PRIMARY CILIUM INCREASES THE INTRACELLULAR CALCIUM CONCENTRATION TRIGGERING A SIGNALING PATHWAY THAT LEADS TO NITRIC OXIDE (NO) FORMATION AND VASODILATION. ADDITIONALLY, CILIOPATHIES, SUCH AS POLYCYSTIC KIDNEY DISEASE AND ATHEROSCLEROSIS, WILL ALSO BE DISCUSSED. WE ALSO ANALYZE AVAILABLE INFORMATION REGARDING A TRIO OF MEMBRANE RECEPTORS INVOLVED IN FSS SENSING AND TRANSDUCING SUCH AS VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTORS (VEGFRS) AND ITS CORECEPTOR NEUROPILIN (NRP), AS WELL AS PURINERGIC RECEPTORS (P2Y2). WHETHER OR NOT THEY MODULATE, THE PRIMARY CILIUM ROLE IN SENSING FSS IS POORLY UNDERSTOOD. THIS CHAPTER HIGHLIGHTS THE MAIN RELEVANCE OF PRIMARY CILIUM IN SENSING BLOOD FLOW, ALTHOUGH EXACT MECHANISMS ARE NOT FULLY KNOWN YET.

OBJECTIVES: ANALYZE WHETHER UMBILICAL CORD PLASMA FROM PREECLAMPTIC PREGNANCIES (U-PE) REDUCES BRAIN ENDOTHELIAL CELL MIGRATION AS AN UNDERLYING MECHANISM OF IMPAIRED BRAIN ANGIOGENESIS. METHODS: HUMAN CEREBRAL MICROVASCULAR ENDOTHELIAL CELLS (HCMEC/D3) WERE INCUBATED (12 H, 1% V/V) WITH UMBILICAL CORD PLASMAS FROM NORMOTENSIVE (N=20, U-NP) OR WOMEN WITH PREECLAMPSIA (N=20, U-PE). CELL VIABILITY (MTT ASSAY), CELL PROLIFERATION (DETECTION OF BROMOURIDINE), AND CELL MIGRATION (WOUND HEALING IN VITRO ASSAY) WERE MEASURED. SYNTHESIS AND RELEASE OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND THE PRESENCE OF ITS RECEPTOR TYPE 2 IN THE INACTIVE (VEGFR2) OR ACTIVE PRO-MIGRATORY PHOSPHORYLATION (Y951-VEGFR2) WERE ANALYZED BY WESTERN BLOT. THE SOLUBLE VEGF RECEPTOR TYPE 1 (OR SFLT-1) WAS MEASURED USING ELISA. ALSO, F-ACTIN POLYMERIZATION/DEPOLYMERIZATION PROTEINS, INCLUDING COFILIN, PHOSPHO-COFILIN, AND ARP2/ARP3 COMPLEX, WERE ANALYZED BY WESTERN BLOT. THE LENGTH AND WIDTH OF F-ACTIN FIBERS (F-ACTIN) WERE EVALUATED USING PHALLOIDIN FLUORESCENCE RESULTS: COMPARED TO PLASMA FROM U-NP, U-PE SIGNIFICANTLY REDUCED CELL PROLIFERATION (P=0.04) AND CELL MIGRATION (P=0.02) WITHOUT AFFECTING CELL VIABILITY. A REDUCTION IN THE VEGFR2 PROTEIN AMOUNT IN BOTH THE INACTIVE AND Y951 PHOSPHORYLATED ISOFORM (PARTICULARLY IN THE CYTOPLASM) WAS FOUND IN CELLS EXPOSED TO U-PE. THIS EFFECT OF U-PE WAS ASSOCIATED WITH REDUCED COFILIN EXPRESSION AND IN THE WIDTH OF F-ACTIN FIBERS, PARTICULARLY IN THE MIDDLE AND TIP SECTIONS OF THE CELLS. IN CONTRAST, NO SIGNIFICANT CHANGES WERE OBSERVED IN THE SYNTHESIS/RELEASE OF VEGF, NEITHER IN THE PLASMA LEVELS NOR THE RELEASE OF SFLT-1. ALSO, NO CHANGES IN PHOSPHO-COFILIN AND ARP2/ARP3 COMPLEX WERE FOUND IN CELLS EXPOSED TO U-PE. CONCLUSION: U-PE LEADS TO REDUCED BRAIN ENDOTHELIAL CELL MIGRATION ASSOCIATED WITH DOWNREGULATION OF THE PRO-MIGRATORY PHOSPHORYLATION OF VEGFR2 AND COFILIN LEVELS THAT MAY LEAD TO HARMED POLYMERIZATION OF F-ACTIN. THESE FINDINGS

BACKGROUND AND PURPOSE: SYSTEMIC INFLAMMATION CONVEYS INFORMATION ABOUT ISCHAEMIC STROKE PROGNOSIS. GROWTH FACTORS WITH NEUROTROPHIC AND ANGIOGENESIS-REGULATING PROPERTIES MIGHT PROVIDE ADDITIONAL INFORMATION ABOUT SEQUELAE. THE PROGNOSTIC PERFORMANCE OF CIRCULATING VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF), PLACENTAL GROWTH FACTOR, INTERLEUKIN 6 AND C-REACTIVE PROTEIN MEASURED AFTER ACUTE ISCHAEMIC STROKE WAS EVALUATED. METHODS: BLOOD SAMPLES WERE COLLECTED FROM N = 45 PATIENTS WITHIN 24-48 H OF ACUTE ISCHAEMIC STROKE. THE PRIMARY OUTCOME WAS DEATH OR MODERATE TO SEVERE DISABILITY AT 6 MONTHS (MODIFIED RANKIN SCALE >2). LOGISTIC REGRESSION MODELS WERE USED TO DETERMINE THE AREA UNDER THE RECEIVER OPERATING CHARACTERISTIC CURVE (AUC). CORRELATION AND PRINCIPAL COMPONENT ANALYSES WERE PERFORMED TO EXAMINE INTERRELATIONSHIPS AMONGST BIOMARKERS. RESULTS: VASCULAR ENDOTHELIAL GROWTH FACTOR WAS ELEVATED IN ISCHAEMIC STROKE PATIENTS WHO DIED OR HAD MODERATE TO SEVERE DISABILITY AT SIX MONTHS. CORRELATION ANALYSIS REVEALED INTERRELATIONSHIPS BETWEEN VEGF AND HBA1C, TRIGLYCERIDES, ERYTHROCYTE SEDIMENTATION RATE AND NATIONAL INSTITUTES OF HEALTH STROKE SCALE AND RANKIN SCORES, WHEREAS PRINCIPAL COMPONENT ANALYSES IDENTIFIED VEGF AS A MAJOR LOADING FACTOR THAT DISCRIMINATED GOOD FROM POOR PROGNOSIS. THERE WERE NO SIGNIFICANT DIFFERENCES IN AUC USING EACH PROTEIN INDIVIDUALLY TO IDENTIFY PATIENTS WHO HAD MODIFIED RANKIN SCALE SCORE >2 AT 6 MONTHS (N = 15/41, AUC 0.61-0.74). HOWEVER, THE AUC INCREASED SIGNIFICANTLY WHEN COMBINING VEGF WITH INTERLEUKIN 6 AND C-REACTIVE PROTEIN COMPARED TO THE VEGF-ONLY MODEL (AUC 0.92 VS. 0.67, P = 0.02). CONCLUSION: CIRCULATING VEGF WAS ELEVATED 24-48 H AFTER ACUTE ISCHAEMIC STROKE AND CONVEYED PROGNOSTIC INFORMATION ABOUT MODERATE TO SEVERE DISABILITY AT 6 MONTHS.