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Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

Journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold Jenifer Murphy-Smith Chee H.Ng David Mischoulon Gerard J.Byrne Chad A.Bousman Con Stough Michael Berk Jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression Clinical and research Program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia Departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Psychiatry the University of MelbourneMelbourne 3052Australia Centre for Human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical Health and Clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The Centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo Depression Nutraceutical Psychiatry

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Age as a predictor of clinical outcomes and determinant of therapeutic measures for emergency medical services treated cardiogenic shock

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Journal of Geriatric Cardiology 2023年第1期20卷 1-10页

作者： Xiaoman Xiao Jason E Bloom Emily Andrew Luke P Dawson Ziad Nehme Michael Stephenson David Anderson Himawan Fernando Samer Noaman Shelley Cox William Chan David M Kaye Karen Smith Dion Stub Department of Cardiology Alfred Health55 Commercial RoadMelbourneAustralia Baker Heart and Diabetes Institute 75 Commercial RoadMelbourneAustralia Department of Cardiology Western HealthFurlong RoadSt AlbansAustralia Ambulance Victoria 31 Joseph StreetBlackburnAustralia School of Public Health and Preventive Medicine Monash University553 St Kilda RoadMelbourneAustralia Department of Paramedicine Monash UniversityMcMahons RoadFrankstonAustralia

BACKGROUND The impact of age on outcomes in cardiogenic shock(CS)is poorly described in the pre-hospital *** assessed the impact of age on outcomes of patients treated by emergency medical services(EMS).METHODS This population-based cohort study included consecutive adult patients with CS transported to hospital by *** linked patients were stratified into tertiles by age(18-63,64-77,and>77 years).Predictors of 30-day mortality were assessed through regression *** primary outcome was 30-day all-cause *** A total of 3523 patients with CS were successfully linked to state health *** average age was 68±16 years and 1398(40%)were *** patients were more likely to have comorbidities including pre-existing coronary artery disease,hypertension,dyslipidemia,diabetes mellitus,and cerebrovascular *** incidence of CS was significantly greater with increasing age(incidence rate per 100,000 person years 6.47[95%CI:6.1-6.8]in age 18-63 years,34.34[32.4-36.4]in age 64-77 years,74.87[70.6-79.3]in age>77 years,P77 years had increased risk of 30-day mortality(adjusted hazard ratio=2.26[95%CI:1.96-2.60]).Older patients were less likely to receive inpatient coronary *** Older patients with EMS-treated CS have significantly higher rates of short-term *** reduced rates of invasive interventions in older patients underscore the need for further development of systems of care to improve outcomes for this patient group.

关键词： assessed services shock

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The impact of height-adjustable desks and classroom prompts on classroom sitting time,social,and motivational factors among adolescents

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Journal of Sport and Health Science 2023年第1期12卷 97-105页

作者： Bronwyn Sudholz Ana Marıa Contardo Ayala Anna Timperio David W.Dunstan David E.Conroy Gavin Abbott Bernie Holland Lauren Arundell Jo Salmon Pomegranate Community Mental Health St John of God Social OutreachBallaratVIC 3350Australia Institute for Physical Activity and Nutrition(IPAN) School of Exercise and Nutrition SciencesDeakin UniversityGeelongVIC 3128Australia Physical Activity Laboratory Baker Heart and Diabetes InstituteMelbourneVIC 3004Australia Mary MacKillop Institute for Health research Australian Catholic UniversityMelbourneVIC 3000Australia Department of Kinesiology Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Preventive Medicine Northwestern UniversityChicagoIL 60611USA The Australian Council for Health and Physical Education and Recreation AbbotsfordVIC 3067Australia

Purpose:This quasi-experimental study examined the impact of height-adjustable desks in combination with prompts to break up prolonged sitting time during class time and identified social and motivational factors associated with breaking up sitting time among ***’perceptions of strategies were also ***:Over 17 weeks,1 classroom in a government secondary school in Melbourne,Australia,was equipped with 27 height-adjustable desks and prompts(posters and desk stickers)to break up classroom sitting *** received professional development in the use of the desks and *** group of adolescents(n=55)had 2-5 lessons/week using the height-adjustable desks in an intervention classroom,and a comparison group matched by year level and subject(n=50)was taught in traditional“seated”*** wore an activPAL monitor at baseline(T0),4 weeks(T1),and 17 weeks(T2)and completed a survey at T0 and *** teachers participated in interviews at *** sizes were calculated(d).Results:Linear mixed models found that,compared to the traditional“seated”classrooms,the adolescents in the intervention classroom had significantly lower sitting time(T1:-9.7 min/lesson,d=-0.96;T2:-6.7 min/lesson,d=-0.70)and time spent in sitting bouts>15 min(T2:-11.2 min/lesson,d=-0.62),and had significantly higher standing time(T1:7.3 min/lesson,d=0.84;T2:5.8 min/lesson,d=0.91),number of breaks from sitting(T1:1.3 breaks/lesson,d=0.49;T2:1.8 breaks/lesson,d=0.67),and stepping time(T1:2.5 min/lesson,d=0.66).Intervention classroom adolescents reported greater habit strength(d=0.58),self-efficacy for breaking up sitting time(d=0.75),and indicated that having a teacher/classmate remind them to stand as helpful(d=0.50).Conclusion:This intervention shows promise for targeting sitting behaviors in the classroom and indicates that incorporating social and motivational strategies may further enhance outcomes.

关键词： Adolescent School Sedentary behavior Sitting Standing

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Patient-specific monocyte-derived microglia as a screening tool for neurodegenerative diseases

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Neural Regeneration research 2023年第5期18卷 955-958页

作者： Hazel Quek Anthony R.White Mental Health and Neuroscience QIMR Berghofer Medical Research Institute School of Biomedical Science The University of QueenslandBrisbaneQLDAustralia

Microglia, the main driver of neuroinflammation, play a central role in the initiation and exacerbation of various neurodegenerative diseases and are now considered a promising therapeutic target. Previous studies on in vitro human microglia and in vivo rodent models lacked scalability, consistency, or physiological relevance, which deterred successful therapeutic outcomes for the past decade. Here we review human blood monocyte-derived microglia-like cells as a robust and consistent approach to generate a patient-specific microglia-like model that can be used in extensive cohort studies for drug testing. We will highlight the strength and applicability of human blood monocyte-derived microglia-like cells to increase translational outcomes by reviewing the advantages of human blood monocyte-derived microglia-like cells in addressing patient heterogeneity and stratification, the basis of personalized medicine.

关键词： human in vitro microglia models neurodegeneration neuroinflammation patient heterogeneity patient stratification peripheral blood monocyte-derived microglia-like cells therapeutic target transdifferentiation translational outcomes

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Does light-intensity physical activity moderate the relationship between sitting time and adiposity markers in adolescents?

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Journal of Sport and Health Science 2022年第5期11卷 613-619页

作者： Ana María Contardo Ayala Jo Salmon David W.Dunstan Lauren Arundell Anna Timperio Institute for Physical Activity and Nutrition(IPAN) School of Exercise and Nutrition SciencesDeakin UniversityGeelongVIA 3125Australia Physical Activity Laboratory Baker Heart and Diabetes InstituteMelbourneVIA 3004Australia Mary MacKillop Institute for Health research Australian Catholic UniversityMelbourneVIA 3000Australia

Background:While the relationship between sedentary time and adiposity markers may be independent of moderate-to-vigorous intensity physical activity(MVPA) among adolescents,little is known about the role of light-intensity physical activity(LIPA) in this *** aim of this cross-sectional study was to examine whether device-measured LIPA and MVPA moderate the associations between objectively measured sitting time and adiposity markers(body mass index(BMI)) and waist circumference(WC)) among ***:This study included accelerometer and inclinometer data obtained from 219 adolescents(age=14.9±1.6 years,mean± SD),collected during 2014 and 2015 in Melbourne,*** GT3 X accelerometers were used to determine time spent in total-LIPA(101 counts/min to 3.99 metabolic equivalents(METs)) was dichotomized into low-LIPA(101-799 counts/min) and high LIPA(800 counts/min to 3.99 METs),and MVPA(> 4 METs).The average time spent sitting was obtained from activPAL *** measures were assessed by trained *** between sitting and total-LIPA,low-LIPA,high-LIPA,and MVPA on BMI z-score(zBMI) and WC z-score(zWC),respectively,were examined using linear regression,adjusting for age and sex;and moderation by total-LIPA,low-LIPA,high-LIPA,and MVPA were examined by adding interaction *** interaction effects were probed by comparing associations at the mean and at 1 SD below and above the ***:Total-LIPA significantly moderated the association between sitting time and zBMI,and low-LIPA significantly moderated the association between sitting time and zBMI and *** other associations were found for total-LIPA,high-LIPA,or ***,at high levels of total-LIPA(+1 SD),there is a negative association between sitting time and *** addition,at high levels of low-LIPA(+1 SD),there is a negative association between sitting time and zBMI and ***:Associations between sitting and adiposit

关键词： Adolescents Anthropometric measures Obesity Physical activity Sedentary behavior Sitting time

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Protein synthesis,degradation,and energy metabolism in T cell immunity

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Cellular & Molecular Immunology 2022年第3期19卷 303-315页

作者： Julia M.Marchingo Doreen A.Cantrell Cell Signalling and Immunology Division School of Life SciencesUniversity of DundeeDundeeDD15EHUK

T cell activation,proliferation,and differentiation into effector and memory states involve massive remodeling of T cell size and molecular content and create a massive increase in demand for energy and amino *** synthesis is an energy-and resource-demanding process;as such,changes in T cell energy production are intrinsically linked to proteome *** this review,we discuss how protein synthesis and degradation change over the course of a T cell immune response and the crosstalk between these processes and T cell energy *** highlight how the use of high-resolution mass spectrometry to analyze T cell proteomes can improve our understanding of how these processes are regulated.

关键词： T lymphocyte Protein Translation Proteomics Immunometabolism Protein degradation

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Can physical activity eliminate the mortality risk associated with poor sleep?A 15-year follow-up of 341,248 MJ Cohort participants

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Journal of Sport and Health Science 2022年第5期11卷 596-604页

作者： Li-Jung Chen Mark Hamer Yun-Ju Lai Bo-Huei Huang Po-Wen Ku Emmanuel Stamatakis Department of Exercise Health Science (National)Taiwan University of SportTaichung 40404China Institute of Sport Exercise and Health Division of Surgery and Interventional ScienceFaculty of Medical SciencesUniversity College LondonLondonWC1E 6BTUK Division of Endocrinology and Metabolism Department of Internal MedicinePuli Branch of Taichung Veterans General HospitalNantou 54552China School of Medicine (National)Yang-Ming UniversityTaipei 11221China Charles Perkins Centre School of Health SciencesFaculty of Medicine and HealthUniversity of SydneySydneyNSW 2006Australia Graduate Institute of Sports and Health (National)Changhua University of EducationChanghua 50007China Department of Kinesiology (National)Tsing Hua UniversityHsinchu 30013China

Background:This study examined the joint associations of sleep patterns and physical activity(PA) with all-cause,cardiovascular disease(CVD),and cancer ***:A total of 341,248 adults(mean age=39.7 years;men:48.3%) were included in the study,with a 15-year *** reported sleep duration and disturbances(difficulty falling asleep,easily awakened,or use of sleeping medication).PA was classified into 4 levels:30.0 metabolic equivalent hours per week(MET-h/week).To understand the joint associations of sleep patterns and PA with mortality,Cox proportional hazard models were conducted,with exposure variables combining sleep duration/disturbances and ***:Compared with the reference group(sleeping 6-8 h/day),individuals who slept>8 h/day had higher risk for all-cause mortality(hazard ratio(HR)=1.307,95% confidence interval(95%CI):1.248-1.369),CVD mortality(HR=1.298,95%CI:1.165-1.445),and cancer mortality(HR=1.128,95%CI:1.042-1.220).Short sleep duration was not associated with mortality *** risk of all-cause and CVD mortality was found in participants who had difficulty falling asleep(HR=1.120,95%CI:1.068-1.175;HR=1.163,95%CI:1.038-1.304,respectively),and used sleeping medication(HR=1.261,95%CI:1.159-1.372;HR=1.335,95%CI:1.102-1.618,respectively) compared with those who slept *** sleep duration and sleep disturbances were not associated with risk of all-cause and CVD mortality among individuals achieving a PA level of>15 MET-h/week,and in particular among those achieving> 30 MET-h/***:Long sleep duration,difficulty falling asleep,and use of sleeping medication were related to a higher risk of *** physically active at a moderate intensity for 25-65 min/day eliminated these detrimental associations.

关键词： Exercise Heart disease Inactivity Insomnia Sleep disorders

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DNA extraction from fresh-frozen and formalin-fixed, paraffinembedded human brain tissue

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Neuroscience Bulletin 2013年第5期29卷 649-654页

作者： Jian-Hua Wang Amany Gouda-Vossos Nicolas Dzamko Glenda Halliday Yue Huang Neuroscience research Australia and the University of New South Wales Department of Neurology Hebei General Hospital

Both fresh-frozen and formalin-fixed,paraffinembedded（FFPE）human brain tissues are invaluable resources for molecular genetic studies of central nervous system diseases,especially neurodegenerative *** identify the optimal method for DNA extraction from human brain tissue,we compared methods on differently-processed *** of LRRK2 and MAPT（257 bp and 483 bp/245 bp）were amplified for *** found that for FFPE samples,the success rate of DNA extraction was greater when using a commercial kit than a laboratory-based method（successful DNA extraction from 76%versus 33%of samples）.PCR amplicon size and storage period were key factors influencing the success rate of DNA extraction from FFPE *** the fresh-frozen samples,the DNA extraction success rate was 100%using either a commercial kit（QIAamp DNA Micro）or a laboratorybased method（sample boiling in 0.1 mol/L NaOH,followed by proteinase K digestion,and then DNA extraction using Chelex-100）regardless of PCR amplicon length or tissue storage *** the present results demonstrate that PCR-amplifiable genomic DNA can be extracted from both fresh-frozen and FFPE samples,fresh brain tissue is recommended for DNA extraction in future neuropathological studies.

关键词： DNA extraction fresh-frozen human brain tissue formalin-fixed paraffin-embedded human brain tissue polymerase chain reaction amplification

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Macroautophagy in sporadic and the genetic form of Parkinson’s disease with the A53T asynuclein mutation

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Translational Neurodegeneration 2012年第1期1卷 4-10页

作者： Yue Huang Fariba Chegini Germaine Chua Karen Murphy Weiping Gai Glenda M Halliday Neuroscience research Australia and the University of New South Wales Sydney2031Australia Department of Human Physiology and the Centre for Neuroscience Flinders University School of MedicineBedford ParkSA5042Australia

Background:The A53T mutation in the a-synuclein gene causes autosomal-dominant Lewy body Parkinson’s disease(PD).Cultured cell models have linked this mutation to increased cell macroautophagy,although evidence of enhanced macroautophagy in patients with this mutation has not been ***:To determine whether macroautophagy is increased by the A53T a-synuclein gene mutation in PD patients and cell ***:Formalin-fixed paraffin-embedded 10μm-thick tissue sections from the substantia nigra and anterior cingulate cortex of two PD patients with the A53T a-synuclein gene mutation were compared with four sporadic PD cases and four controls obtained from the Sydney Brain *** bodies were isolated from frontal cortex of a case with late stage PD(recruited from South Australian Brain Bank).Immunohistochemistry was performed for a-synuclein and the macroautophagy markers autophagy-specific gene(ATG)5,ATG6/Beclin1 and ATG8/***5Y cells were transfected with wild type or A53T mutant a-synuclein plasmids and observable changes in macroautophagy marker protein levels assessed using Western ***:a-Synuclein immunoreactive neurites and dots were more numerous in patients with A53T mutations compared with late stage sporadic PD patients,and perinuclear cytoplasmic a-synuclein aggregates were observed in the a-synuclein A53T gene transfected SH-SY5Y cells compared to wild type *** PD patients(with or without A53T mutations)had increased immunohistochemical evidence for macroautophagy compared with controls,and the levels of the ATG5 complex were equally increased in wild type and A53T a-synuclein gene transfected cells compared to ***:Despite increased a-synuclein accumulation with A53T mutations,macroautophagy is not increased above that observed in sporadic patients with PD or in cells transfected with wild type a-synuclein,suggesting that mutated a-synuclein protein is not removed by macroautophagy.

关键词： α-synuclein macroautophagy Parkinson’s disease

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Can we clinically diagnose dementia with Lewy bodies yet?

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Translational Neurodegeneration 2013年第1期2卷 17-25页

作者： Yue Huang Glenda Halliday Neuroscience research Australia The University of New South WalesSydneyNSW 2031Australia

Dementia with Lewy Bodies(DLB)was initially identified and confirmed primarily by pathology,but is soon to be incorporated into the Diagnostic and Statistical Manual criteria as a clinical disease *** these advances over more than 20 years,current data suggest that the sensitivity of accurate clinical diagnosis of DLB is still very low,although there is mounting evidence that supportive features may increase diagnostic *** DLB remains easy to identify pathologically with different cellular pathologies differentiating it from other dementia syndromes,pathological identification using only Lewy body pathology has been shown to be inaccurate due to overlap with patients without dementia symptoms.A number of studies now suggest that a combination of cellular pathologies,which include α-synuclein and β-amyloid deposition as well as dopamine denervation,assist with differentiating this dementia syndrome from *** clinical and pathological overlap with the tauopathy of Alzheimer’s disease still remains to be *** determine more robust and independent clinicopathological correlates from Alzheimer’s disease,longitudinal prospective studies,using specific clinical batteries on dementia patients reaching the proposed criteria for DLB,with post-mortem assessment of the multiple pathologies associated with dementia,are *** genetic causes for DLB is another approach to investigate the pathogenesis of *** this approach has been hindered to date by difficulties with identifying DLB *** use of novel techniques is likely to advance knowledge on the pathogenesis of DLB and assist with redefining clinical and pathologic diagnostic *** achieve the goal of more accurate clinical diagnosis of DLB,breakthroughs are necessary on the pathogenesis of DLB.

关键词： Dementia with Lewy bodies Diagnosis Genetics Pathogenesis Pathology

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