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World Journal of Pediatric Surgery 2024年第1期7卷 59-65页

作者： Abirami Muthumani CSF Center for Health Equity in Surgery and Anesthesia Universityof California San FranciscoSan FranciscoCaliforniaUSA Department of General Surgery Columbia University Irving Medical CenterNewYorkNew YorkUSA

INTRODUCTION Pediatric surgical interventions may represent more than one-third of the surgical caseload in humanitarian settings.1 The humanitarian crisis in Gaza has taken a devastating toll on children,many of whom have suffered injuries due to indiscriminate and heavy bombardment,resulting in severe polytraumatic injuries necessitating immediate and specialized pediatric surgical intervention.The conflict has strained the region's fragile healthcare system,resulting in a significant number of casualties,a substantial proportion of which are children.This exacerbates the demand for specialized pediatric surgical care,especially when the existing healthcare system and infrastructure has nearly collapsed and is under-resourced to handle the influx of pediatric patients.2 The urgency for specialized pediatric surgical care and support for children in Gaza cannot be overstated.Access to healthcare in Palestine has been an ongoing challenge.

关键词： pediatric injuries surgical

Dynamic transcriptional programs define distinct mammalian cortical lineages

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Neural Regeneration Research 2024年第2期19卷 387-389页

作者： Tanzila Mukhtar Verdon Taylor Department of Biomedicine University of BaselBaselSwitzerland Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research University of CaliforniaSan FranciscoCAUSA

The cerebral cortex is composed of billions of neurons and glia that are generated sequentially during corticogenesis.These cells are generated in an organized fashion during development.At early stages of brain devel... 详细信息

关键词： cortex cerebral development

Matrix metalloproteinases and their expression in mammary gland

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Cell Research 1998年第3期8卷 187-194页

作者： URIA JOSE A ZENA WERB(Department of Anatomy, university of california san francisco, CA 94143-0452, USA) Department of Anatomy University of California San Francisco CA USA

The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play a key role in both normal and pathological processes involving tissue remodeling events. The expression of these proteolytic enzymes is highly regulated by a balance between extracellular matrix (ECM) deposition and its degradation, and is controlled by growth factors, cytokines, hormones, as well as interactions with the ECM macromolecules. Furthermore, the activity of the MMPs is regulated by their natural endogenous inhibitors, which are members of the tissue inhibitor of metalloproteinases (TIMP) family. In the normal mammary gland, MMPs are expressed during ductal development, lobulo-alveolar development in pregnancy and involution after lactation. Under pathological conditions, such as tumorigenesis, the dysregulated expression of MMPs play a role in tumor initiation, progression and malignant conversion as well as facilitating invasion and motastasis of malignant cells through degradation of the ECM and basement membranes. Matrix metalloproteinases and their expression in mammary gland

关键词： Matrix metalloproteinases ECM cancer progression mammary gland

Crafting chirality in three dimensions via a novel fabrication technique for bound states in the continuum metasurfaces

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Light(Science & Applications) 2024年第3期13卷 390-392页

作者： Zaid Haddadin Anna My Nguyen Lisa V.Poulikakos Department of Electrical&Computer Engineering University of California San DiegoLa JollaCAUSA Department of Mechanical&Aerospace Engineering University of California San DiegoLa JollaCAUSA Program of Materials Science&Engineering University of California San DiegoLa JollaCAUSA

An additional deposition step was added to a multi-step electron beam lithographic fabrication process to unlock the height dimension as an accessible parameter for resonators comprising unit cells of quasi-bound stat... 详细信息

关键词： dimensions dimension intrinsic

Aging impairs the osteocytic regulation of collagen integrity and bone quality

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Bone Research 2024年第1期12卷 78-94页

作者： Charles A.Schurman Serra Kaya Neha Dole Nadja M.Maldonado Luna Natalia Castillo Ryan Potter Jacob P.Rose Joanna Bons Christina D.King Jordan B.Burton Birgit Schilling Simon Melov Simon Tang Eric Schaible Tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley/UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Buck Institute for Research on Aging NovatoCA 94945USA Washington university in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly individuals.The molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by osteocytes.We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material properties.We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses PLR.The control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)bone.This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests.The effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity

SARS-CoV-2 variants are associated with different clinical courses in children with MIS-C

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World Journal of Pediatrics 2024年第2期20卷 143-152页

作者： Andres F.Moreno Rojas Emelia Bainto Helen Harvey Adriana H.Tremoulet Jane C.Burns Kirsten B.Dummer Department of Pediatrics Division of Pediatric CardiologyUniversity of California San Diegoand Rady Children’s Hospital3020 Children’s Way MC 5004San DiegoCA 92123USA Kawasaki Disease Research Center La JollaCAUSA Department of Pediatrics Division of Pediatric Critical CareUniversity of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA Department of Pediatrics University of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA

Background Recent infection with SARS‑CoV-2 in children has been associated with multisystem inflammatory syndrome in children(MIS-C).SARS‑CoV-2 has undergone different mutations.Few publications exist about specific variants and their correlation with the severity of MIS-C.Methods This was a single-center,retrospective study including all patients admitted with MIS-C at Rady Children’s Hospital-san Diego between May 2020 and March 2022.Local epidemiologic data,including viral genomic information,were obtained from public records.Demographics,clinical presentation,laboratory values,and outcomes were obtained from electronic medical records.Results The analysis included 104 pediatric patients.Four MIS-C waves were identified.Circulating variants in san Diego during the first wave included clades 20A to C.During the second wave,there were variants from clades 20A to C,20G,21C(Epsilon),20I(Alpha),and 20J(Gamma).The third wave had Delta strains(clades 21A,21I,and 21J),and the fourth had Omicron variants(clades 21K,21L,and 22C).MIS-C presented with similar symptoms and laboratory findings across all waves.More patients were admitted to the pediatric intensive care unit(PICU)(74%)and required inotropic support(63%)during the second wave.None of the patients required mechanical circulatory support,and only two required invasive ventilatory support.There was no mortality.Conclusions The various strains of SARS-CoV-2 triggered MIS-C with differing severities,with the second wave having a more severe clinical course.Whether the differences in disease severity across variants were due to changes in the virus or other factors remains unknown.

关键词： Complications COVID-19 MIS-C SARS-CoV-2 variants

A lead role for a“secondary”axonal injury response

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Neural Regeneration Research 2025年第2期20卷 469-470页

作者： Melissa A.Rudy Trent A.Watkins Division of Neuroimmunology and Glial Biology Department of NeurologyUniversity of California at San FranciscoSan FranciscoCAUSA Development Disease Modelsand Therapeutics Graduate ProgramBaylor College of MedicineHoustonTXUSA

Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in non-regenerative environments.This duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative potential.This dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve crush.In this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).

关键词： injury axonal stress

Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics:The Study of Muscle,Mobility and Aging(SOMMA)

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Journal of Sport and Health Science 2024年第5期13卷 621-630页

作者： Yujia(Susanna)Qiao Terri L.Blackwell Peggy M.Cawthon Paul M.Coen Steven R.Cummings Giovanna Distefano Samaneh Farsijani Daniel E.Forman Bret H.Goodpaster Stephen B.Kritchevsky Theresa Mau Frederico G.S.Toledo Anne B.Newman Nancy W.Glynn Department of Epidemiology School of Public HealthUniversity of PittsburghPittsburghPA 15261USA san francisco Coordinating Center California Pacific Medical Center Research InstituteSan FranciscoCA 94143USA Department of Epidemiology and Biostatistics University of CaliforniaSan FranciscoCA 94143USA Translational Research Institute AdventHealthOrlandoFL 32804USA Department of Medicine(Geriatrics and Cardiology) University of Pittsburghand GeriatricsResearchEducationand Clinical Center(GRECC)VA Pittsburgh Healthcare SystemPittsburghPA 15261USA Department of Internal Medicine Section on Gerontology and Geriatric MedicineWake Forest School of MedicineWinston-SalemNC 27109USA Division of Endocrinology and Metabolism Department of MedicineUniversity of PittsburghPittsburghPA 15261USA

Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older adults.Yet,many studies reporting these effects were based on self-reported PA or structured exercise interventions.Therefore,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics.Methods:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 days.Self-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)questionnaire.Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary behavior.As a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics.Results:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(p<0.05).Light activity was not associated with maxOXPHOS or ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.006 mM/s lower ATP_(max)(p<0.05).Only associatio

关键词： Aging Exercise Mitochondria

Combining neural progenitor cell transplant and rehabilitation for enhanced recovery after cervical spinal cord injury

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Neural Regeneration Research 2024年第7期19卷 1433-1434页

作者： Camila M.Freria Paul Lu Department of Neurosciences University of CaliforniaSan DiegoLa JollaCAUSA Veterans Administration san Diego Healthcare System San DiegoCAUSA

Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control in humans.This system has historically been the most refractory to regenerative efforts after SCI.The "nonregeneration" of the CST changed when robust regeneration of the CST into spared tissue was demonstrated by the inactivation of phosphatase and tensin homolog and delivery of inosine.

关键词： cervical progenitor injury

Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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Journal of Sport and Health Science 2024年第5期13卷 611-620页

作者： Benjamin T.Schumacher Michael J.LaMonte Andrea Z.LaCroix Eleanor M.Simonsick Steven P.Hooker Humberto Parada Jr. John Bellettiere Arun Kumar Herbert Wertheim School of Public Health and Human Longevity Science University of California San DiegoLa JollaCA 92093USA Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA Translational Gerontology Branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human Services San Diego State UniversitySan DiegoCA 92182USA Division of Epidemiology and Biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA university of california san Diego Moores Cancer Center La JollaCA 92093USA Computer Science and Engineering and Halicioglu Data Science Institute University of California San DiegoLa JollaCA 92093USA

Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older adults.Since direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction algorithms.Methods:The Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)values.We developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging cohorts.Finally,we quantified the associations between measured and predicted VO_(2max)and mortality.Results:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/min.Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,respectively.Incremental quartiles of measured VO_(2max)showed an inverse gradient in mortality risk.Predicted VO_(2max)variables yielded similar effect estimates but were not robust to adjustment.Conclusion:Measured VO_(2max)is a strong predictor of mortality.Using ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to adjustment.Future studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： Cardiorespiratory fitness Prediction algorithms Epidemiology Mortality