Tissue engineering allows the design of functionally active cells within supportive bio-scaffolds to promote the development of new tissues such as cartilage and bone for the restoration of pathologically altered tiss...Tissue engineering allows the design of functionally active cells within supportive bio-scaffolds to promote the development of new tissues such as cartilage and bone for the restoration of pathologically altered tissues. However, all bone tissue engineering applications are limited by a shortage of stem cells. The adult bone marrow stroma contains a subset of nonhematopoietic cells referred to as bone marrow mesenchymal stem cells （BMSCs）. BMSCs are of interest because they are easily isolated from a small aspirate of bone marrow and readily generate singlecell-derived colonies. These cells have the capacity to undergo extensive replication in an undifferentiated state ex vivo. In addition, BMSCs have the potential to develop either in vitro or in vivo into distinct mesenchymal tissues,including bone, cartilage, fat, tendon, muscle, and marrow stroma. Thus, BMSCs are an attractive cell source for tissue engineering approaches. However, BMSCs are not homogeneous and the quantity of stem cells decreases in the bone marrow in aged population. A sequential loss of lineage differentiation potential has been found in the mixed culture of bone marrow stromal cells due to a heterogenous popu- lation. Therefore, a number of studies have proposed that homogenous bone marrow stem cells can be generated from clonal culture of bone marrow cells and that BMSC clones have the greatest potential for the application of bone regeneration in vivo.展开更多
Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells （DPSCs） for potential application in tendon tissue engin...Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells （DPSCs） for potential application in tendon tissue engineering. The expression of tendon- related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid （PGA） fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a ootential stem cell source for tissue enEineerin~ of tendon-like tissue.展开更多
While stromal interactions are essential in cancer adaptation to hormonal therapies,the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood.Here,we tissue-engineered and...While stromal interactions are essential in cancer adaptation to hormonal therapies,the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood.Here,we tissue-engineered and validated an in vitro microtissue model of osteoblastic bone metastases,and used it to study the effects of androgen deprivation in this microenvironment.The model was established by culturing primary human osteoprogenitor cells on melt electrowritten polymer scaffolds,leading to a mineralized osteoblast-derived microtissue containing,in a 3D setting,viable osteoblastic cells,osteocytic cells,and appropriate expression of osteoblast/osteocyte-derived mRNA and proteins,and mineral content.Direct co-culture of androgen receptordependent/ independent cell lines (LNCaP,C4-2B,and PC3) led cancer cells to display functional and molecular features as observed in vivo.Co-cultured cancer cells showed increased affinity to the microtissues,as a function of their bone metastatic potential.Cocultures led to alkaline phosphatase and collagen-I upregulation and sclerostin downregulation,consistent with the clinical marker profile of osteoblastic bone metastases.LNCaP showed a significant adaptive response under androgen deprivation in the microtissues,with the notable appearance of neuroendocrine transdifferentiation features and increased expression of related markers (dopa decarboxylase,enolase 2).Androgen deprivation affected the biology of the metastatic microenvironment with stronger upregulation of androgen receptor,alkaline phosphatase,and dopa decarboxylase,as seen in the transition towards resistance.The unique microtissues engineered here represent a substantial asset to determine the involvement of the human bone microenvironment in prostate cancer progression and response to a therapeutic context in this microenvironment.展开更多
AIM To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on wholebody and hepatic fat oxidation of patients with nonalcoholic fatty liver disease(NAFLD).METHODS Participant...AIM To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on wholebody and hepatic fat oxidation of patients with nonalcoholic fatty liver disease(NAFLD).METHODS Participants were randomised into either circuit exercise training(EX;n = 13;3 h/wk without changes in dietary habits),or dietary energy restriction(ER) without changes in structured physical activity(ER;n = 8).Respiratory quotient(RQ) and whole-body fat oxidation rates(Fatox) were determined by indirect calorimetry under basal,insulin-stimulated and exercise conditions.Severity of disease and steatosis was determined by liver histology;hepatic Fatox was estimated from plasma β-hydroxybutyrate co.ncentrations;cardiorespiratory fitness was expressed as VO2 peak.Complete-case analysis was performed(EX:n = 10;ER:n = 6).RESULTS Hepatic steatosis and NAFLD activity score decreased with ER but not with EX.β-hydroxybutyrate concentrations increased significantly in response to ER(0.08 ± 0.02 mmol/L vs 0.12 ± 0.04 mmol/L,P = 0.03) but remained unchanged in response to EX(0.10 ± 0.03 mmol/L vs 0.11 ± 0.07 mmol/L,P = 0.39).Basal RQ decreased(P = 0.05) in response.to EX,while this change was not significant after ER(P = 0.38).VO_(2peak)(P < 0.001) and maximal Fa_(tox) during aerobic exercise(P = 0.03) improved with EX but not with ER(P > 0.05).The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis(r =-0.56,P = 0.04).CONCLUSION ER and EX lead to specific benefits on fat metabolism of patients with NAFLD.Increased hepatic Fat_(ox) in response to ER could be one mechanism through which the ER group achieved reduction in steatosis.展开更多
Advanced prostate cancer(PCa)is known for its high prevalence to metastasize to bone,at which point it is considered incurable.Despite significant effort,there is no animal model capable of recapitulating the complexi...Advanced prostate cancer(PCa)is known for its high prevalence to metastasize to bone,at which point it is considered incurable.Despite significant effort,there is no animal model capable of recapitulating the complexity of PCa bone metastasis.The humanized mouse model for PCa bone metastasis used in this study aims to provide a platform for the assessment of new drugs by recapitulating the human–human cell interactions relevant for disease development and progression.The humanized tissueengineered bone construct(hTEBC)was created within NOD-scid IL2rgnull(NSG)mice and was used for the study of experimental PC3-Luc bone metastases.It was confirmed that PC3-Luc cells preferentially grew in the hTEBC compared with murine bone.The translational potential of the humanized mouse model for PCa bone metastasis was evaluated with two clinically approved osteoprotective therapies,the non-species-specific bisphosphonate zoledronic acid(ZA)or the human-specific antibody Denosumab,both targeting Receptor Activator of Nuclear Factor Kappa-ΒLigand.ZA,but not Denosumab,significantly decreased metastases in hTEBCs,but not murine femora.These results highlight the importance of humanized models for the preclinical research on PCa bone metastasis and indicate the potential of the bioengineered mouse model to closely mimic the metastatic cascade of PCa cells to human bone.Eventually,it will enable the development of new effective antimetastatic treatments.展开更多
We sought to evaluate central corneal thickness（CCT）,corneal endothelial cell density（ECD）and intraocular pressure（IOP）in patients with type 2 diabetes mellitus（DM）and to associate potential differences with d...We sought to evaluate central corneal thickness（CCT）,corneal endothelial cell density（ECD）and intraocular pressure（IOP）in patients with type 2 diabetes mellitus（DM）and to associate potential differences with diabetes duration and treatment modality in a prospective,randomized study.We measured ECD,CCT and IOP of125 patients with type 2 DM（mean age 57.1±11.5 years）and compared them with 90 age-matched controls.Measured parameters were analyzed for association with diabetes duration and glucose control modalities（insulin injection or oral medication）while controlling for age.In the diabetic group,the mean ECD（2511±252 cells/mm^2）,mean CCT（539.7±33.6μm）and mean IOP（18.3±2.5 mmHg）varied significantly from those the control group[ECD：2713±132 cells/mm^2（P〈0.0001）,CCT：525.0±45.3μm（P=0.003）and IOP：16.7±1.8 mmHg（P〈0.0001）].ECD was significantly reduced by about 32 cell/mm^2 for diabetics with duration of〉10 years when compared with those with duration of〈10 years（P〈0.05）.CCT was thicker and IOP was higher for diabetics with duration of〉10 years than those with duration of〈10 years（P〉0.05）.None of the measured parameters was significantly associated with diabetes duration and treatment modality（P〉0.05）.In conclusion,subjects with type 2DM exhibit significant changes in ECD,IOP and CCT,which,however,are not correlated with disease duration or if the patients receive on insulin injection or oral medications.展开更多
AIM: To investigate the number of hypertensive patients, the optometrist is able to identify by routinely taking blood pressure(BP) measurements for patients in "at-risk" groups, and to sample patients’ opi...AIM: To investigate the number of hypertensive patients, the optometrist is able to identify by routinely taking blood pressure(BP) measurements for patients in "at-risk" groups, and to sample patients’ opinions regarding in-office BP measurement. Many of the optometrists in Saudi Arabia practice in optical stores.These stores are wide spread, easily accessible and seldom need appointments. The expanding role of the optometrist as a primary health care provider(PHCP) and the increasing global prevalence of hypertension,highlight the need for an integrated approach towards detecting and monitoring hypertension.METHODS: Automated BP measurements were made twice(during the same session) at five selected optometry practices using a validated BP monitor(Omron M6) to assess the number of patients with high BP(HBP)- in at-risk groups-visiting the eye clinic routinely. Prior to data collection, practitioners underwent a two-day training workshop by a cardiologist on hypertension and how to obtain accurate BP readings. A protocol for BP measurement was distributed and retained in all participating clinics. The general,,.,attitude towards cardiovascular health of 480 patients aged 37.2(±12.4)y and their opinion towards in-office BP measurement was assessed using a self-administered questionnaire.RESULTS: A response rate of 83.6% was obtained for the survey. Ninety-three of the 443 patients(21.0%)tested for BP in this study had HBP. Of these,(62subjects) 67.7% were unaware of their HBP status. Thirty of the 105 subjects(28.6%) who had previously been diagnosed with HBP, still had HBP at the time of this study, and only 22(73.3%) of these patients were on medication. Also, only 25% of the diagnosed hypertensive patients owned a BP monitor.CONCLUSION: Taking BP measurements in optometry practices, we were able to identify one previously undiagnosed patient with HBP for every 8 adults tested.We also identified 30 of 105 previously diagnosed patients whose BP was poorly controlled, twenty-two of whom were on medication. The patients who participated in this study were positively disposed toward the routine measurement of BP by optometrists.展开更多
AIM： To examine the prevalence of dyslexia and Meares-Irlen syndrome（MIS） among female students and determine their level of visual stress in comparison with normal subjects.·METHODS： A random sample of 450 f...AIM： To examine the prevalence of dyslexia and Meares-Irlen syndrome（MIS） among female students and determine their level of visual stress in comparison with normal subjects.·METHODS： A random sample of 450 female medical students of King Saud University Riyadh（age range, 18-30y） responded to a wide range of questions designed to accomplish the aims of this study. The detailed questionnaire consisted of 54 questions with 12 questions enquiring on ocular history and demography of participants while 42 questions were on visual symptoms. Items were categorized into critical and non-critical questions（CQ and NCQ） and were rated on four point Likert scale. Based on the responses obtained, the subjects were grouped into normal（control）, dyslexic with or without MIS（Group 1） and subjects with MIS only（Group 2）. Responses were analysed as averages and mean scores were calculated and compared between groups using one way analysis of variance to evaluate total visual stress score（TVSS =NCQ ＋CQ）, critical and non-critical visual stress scores. The relationship between categorical variables such as age, handedness and condition were assessed with Chi-square test.·RESULTS： The completion rate was 97.6% and majority of the respondents（92%） were normal readers, 2%dyslexic and 6% had MIS. They were age-matched. More than half of the participants had visited an eye care practitioner in the last 2y. About 13% were recommendedeye exercises and one participant experienced pattern glare. Hand preference was not associated with any condition but Group 1 subjects（3/9, 33%） were significantly more likely to be diagnosed of lazy eye than Group 2（2/27, 7%） and control（27/414, 7%） subjects. The mean±SD of TVSS responses were 63±14 and it was 44±9for CQ and 19 ±5 for NCQ. Responses from all three variables were normally distributed but the CQ responses were on the average more positive（82%） in Group 2 and less positive（46%） in Group 1 than control. With NCQ,the responses were equally less positive in Group 1 and2 than control. Group 2 subjects showed significantly higher TVSS（P =0.002）, NCQ（P =0.006） and CQ（P =0.008）visual stress scores than control but no difference between Group 1 and control subjects, was observed for all scores（P 〉0.05, for all comparisons）.·CONCLUSION： The prevalence of dyslexia and MIS among Saudi female students was 2% and 6%,respectively. Critical questions performed best for assessing visual stress symptoms in dyslexic and MIS subjects. Generally, students with MIS were more sensitive to visual stress than normal students but dyslexics were more likely to present with a lazy eye than MIS and normal readers.展开更多
This study compared proximal femoral morphology in patients living in soft and hard water regions. The proximal femoral morphology of two groups of 70 patients living in hard and soft water regions with a mean age of ...This study compared proximal femoral morphology in patients living in soft and hard water regions. The proximal femoral morphology of two groups of 70 patients living in hard and soft water regions with a mean age of 72.29 (range: 50 to 87 years) was measured using an antero-posterior radiograph of the non-operated hip with magnification adjusted. The medullary canal diameter at the level of the lesser trochanter (LT) was significantly wider in patients living in the hard water region (mean width: 1.9 mm wider;p = 0.003). No statistical significant difference was found in the medullary canal width at 10 cm below the level of LT, Dorr index, or Canal Bone Ratio (CBR). In conclusion, the proximal femoral morphology does differ in patients living in soft and hard water areas. These results may have an important clinical bearing in patients undergoing total hip replacement surgery. Further research is needed to determine whether implant survivorship is affected in patients living in hard and soft water regions.展开更多
Large scale exome sequencing studies have ＇revealed regions of the genome, which contribute to the castrate resistant prostate cancer （CRPC） phenotype.1-3 Such studies have identified mutations in genes, which may ...Large scale exome sequencing studies have ＇revealed regions of the genome, which contribute to the castrate resistant prostate cancer （CRPC） phenotype.1-3 Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor （AR） and speckle-type POZ protein （SPOP） genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al.4 which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particnlarly in the context of SPOP-mediated degradation of the AR.展开更多
Objective To study the relation between temperature and mortality by estimating the temperature-related mortality in Beijing, Shanghai, and Guangzhou. Methods Data of daily mortality, weather and air pollution in the ...Objective To study the relation between temperature and mortality by estimating the temperature-related mortality in Beijing, Shanghai, and Guangzhou. Methods Data of daily mortality, weather and air pollution in the three cities were collected. A distributed lag nonlinear model was established and used in analyzing the effects of temperature on mortality. Current and future net temperature-related mortality was estimated. Results The association between temperature and mortality was J-shaped, with an increased death risk of both hot and cold temperature in these cities. The effects of cold temperature on health lasted longer than those of hot temperature. The projected temperature-related mortality increased with the decreased cold-related mortality. The mortality was higher in Guangzhou than in Beijing and Shanghai. Conclusion The impact of temperature on health varies in the 3 cities of China, which may have implications for climate policy making in China.展开更多
It is believed that human ancestors evolved the ability to run bipedally approximately 2 million years ago. This form of locomotion may have been important to our survival and likely has influenced the evolution of ou...It is believed that human ancestors evolved the ability to run bipedally approximately 2 million years ago. This form of locomotion may have been important to our survival and likely has influenced the evolution of our body form. As our bodies have adapted to run, it seems unusual that up to 79% of modern day runners are injured annually. The etiology of these injuries is clearly multifactorial. However, 1 aspect of running that has significantly changed over the past 50 years is the footwear we use. Modern running shoes have become increasingly cushioned and supportive, and have changed the way we run. In particular, they have altered our footstrike pattern from a predominantly forefoot strike(FFS) landing to a predominantly rearfoot strike(RFS) landing. This change alters the way in which the body is loaded and may be contributing to the high rate of injuries runners experience while engaged in an activity for which they were adapted. In this paper, we will examine the benefits of barefoot running(typically an FFS pattern),and compare the lower extremity mechanics between FFS and RFS. The implications of these mechanical differences, in terms of injury, will be discussed. We will then provide evidence to support our contention that FFS provides an optimal mechanical environment for specific foot and ankle structures, such as the heel pad, the plantar fascia, and the Achilles tendon. The importance of footwear will then be addressed, highlighting its interaction with strike pattern on mechanics. This analysis will underscore why footwear matters when assessing mechanics. Finally, proper preparation and safe transition to an FFS pattern in minimal shoes will be emphasized. Through the discussion of the current literature, we will develop a justification for returning to running in the way for which we were adapted to reduce running-related injuries.展开更多
Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system ...Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.展开更多
High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the h...High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the healing of bone fractures, and vice versa. Despite this knowledge, most impact trauma studies in animals have focussed on bone fractures or soft tissue trauma in isolation. However, given the simultaneous impact on both tissues a better understanding of the interaction between these two injuries is necessary to optimise clinical treatment. The aim of this study was therefore to develop a new experimental model and characterise, for the first time, the healing of a complex fracture with concurrent closed soft tissue trauma in sheep. A pendulum impact device was designed to deliver a defined and standardised impact to the distal thigh of sheep, causing a reproducible contusion injury to the subcutaneous soft tissues. In a subsequent procedure, a reproducible femoral butterfly fracture (AO C3-type) was created at the sheep’s femur, which was initially stabilised for 5 days by an external fixator construct to allow for soft tissue swelling to recede, and ultimately in a bridging construct using locking plates. The combined injuries were applied to twelve sheep and the healing observed for four or eight weeks (six animals per group) until sacrifice. The pendulum impact led to a moderate to severe circumferential soft tissue injury with significant bruising, haematomas and partial muscle disruptions. Posttraumatic measurements showed elevated intra-compartmental pressure and circulatory tissue breakdown markers, with recovery to normal, pre-injury values within four days. Clinically, no neurovascular deficiencies were observed. Bi-weekly radiological analysis of the healing fractures showed progressive callus healing over time, with the average number of callus bridges increasing from 0.4 at two weeks to 4.2 at eight weeks. Biomechanical testing after sacrifice showed in- creasing torsional stiffness between four and eight weeks healing time from 10% to 100%, and increasing ultimate torsional strength from 10% to 64% (relative to the contralateral control limb). Our results demonstrate the robust healing of a complex femur fracture in the presence of a severe soft tissue contusion injury in sheep and demonstrate the establishment of a clinically relevant experimental model, for research aimed at improving the treatment of bone fractures accompanied by closed soft tissue injuries.展开更多
Background:Overweight and obesity has become a serious public health problem in many parts of the world.Studies suggest that making small changes in daily activity levels such as"breaking-up"sedentary time(i...Background:Overweight and obesity has become a serious public health problem in many parts of the world.Studies suggest that making small changes in daily activity levels such as"breaking-up"sedentary time(i.e.,standing)may help mitigate the health risks of sedentary behavior.The aim of the present study was to examine time spent in standing(determined by count threshold),lying,and sitting postures(determined by inclinometer function)via the ActiGraph GT3X among sedentary adults with differing weight status based on body mass index(BMI)categories.Methods:Participants included 22 sedentary adults(14 men,8 women;mean age 26.5±4.1 years).All subjects completed the self-report International Physical Activity Questionnaire to determine time spent sitting over the previous 7 days.Participants were included if they spent seven or more hours sitting per day.Postures were determined with the ActiGraph GT3X inclinometer function.Participants were instructed to wear the accelerometer for 7 consecutive days(24 h a day).BMI was categorized as:18.5 to【25 kg/m2as normal,25 to【30 kg/m2as overweight,and≥30 kg/m2as obese.Results:Participants in the normal weight(n=10)and overweight(n=6)groups spent significantly more time standing(after adjustment for moderate-to-vigorous intensity physical activity and wear-time)(6.7 h and 7.3 h respectively)and less time sitting(7.1 h and 6.9 h respectively)than those in obese(n=6)categories(5.5 h and 8.0 h respectively)after adjustment for wear-time(p【0.001).There were no significant differences in standing and sitting time between normal weight and overweight groups(p=0.051 and p=0.670 respectively).Differences were not significant among groups for lying time(p=0.55).Conclusion:This study described postural allocations standing,lying,and sitting among normal weight,overweight,and obese sedentary adults.The results provide additional evidence for the use of increasing standing time in obesity prevention strategies.展开更多
Background： It has been reported that strenuous exercise increases the number of bone marrow-derived progenitor cells such as CD34＋ cells in the blood, but no previous studies have investigated the changes in circul...Background： It has been reported that strenuous exercise increases the number of bone marrow-derived progenitor cells such as CD34＋ cells in the blood, but no previous studies have investigated the changes in circulating CD34＋ cells following resistance exercise. This study tested the hypothesis that the number of CD34＋ cells in the blood would increase after eccentric exercise of the elbow flexors, but decrease in recovery, and the magnitude of the changes would be dependent on the magnitude of muscle damage. Methods： Nine men （28.0 ± 6.6 years） performed exercises consisting of 10 sets of six maximal voluntary eccentric contractions of the elbow flexors with their non-dominant arm. Six of them performed the same exercise with the same ann 4 weeks later. Changes in indirect markers of muscle damage were measured before, within 10 min after, and at 24, 48, 72, and 96 h after eccentric exercise. Differential leukocyte counts （total leukocytes, neutrophils, lymphocytes, monocytes） and CD34＋ cells in the blood were measured before, immediately after, and at 2, 24, 48, 72, and 96 h following the exercises. Results： After eccentric exercise, significant （p 〈 0.05） decreases in maximal voluntary isometric contraction torque and increases in delayed onset muscle soreness and plasma creatine kinase activity were observed. However, no significant changes in leukocytes and CD34＋ cells were evident. The changes in muscle damage markers were significantly （p 〈 0.05） smaller following the second exercise session as compared with the first exercise session, but the changes in leukocytes and CD34＋ cells were not significantly different between sessions. Conclusion： These results did not support the hypothesis, and showed that eccentric exercise-induced muscle damage to the elbow flexors did not influence the number of circulating CD34＋ cells.展开更多
AIM To investigate the synergistic hepato-protective properties of curcumin and vitamin E in an Hfe^(-/-)high calorie diet model of steatohepatitis.METHODS Hfe^(-/-)C57BL/6J mice were fed either a high calorie diet or...AIM To investigate the synergistic hepato-protective properties of curcumin and vitamin E in an Hfe^(-/-)high calorie diet model of steatohepatitis.METHODS Hfe^(-/-)C57BL/6J mice were fed either a high calorie diet or a high calorie diet with 1 mg/g curcumin; 1.5 mg/g vitamin E; or combination of 1 mg/g curcumin + 1.5 mg/g vitamin E for 20 wk. Serum and liver tissue were collected at the completion of the experiment. Liver histology was graded by a pathologist for steatosis, inflammation and fibrosis. RNA and protein was extracted from liver tissue to examine gene and protein expression associated with fatty acid oxidation, mitochondrial biogenesis and oxidative stress pathways.RESULTS Hfe^(-/-)mice fed the high calorie diet developed steatohepatitis and pericentral fibrosis. Combination treatment with curcumin and vitamin E resulted in a greater reduction of percent steatosis than either vitamin E or curcumin therapy alone. Serum alanine aminotransferase and non-alcoholic fatty liver disease(NAFLD) activity score were decreased following combination therapy with curcumin and vitamin E compared with high calorie diet alone. No changes were observed in inflammatory or fibrosis markers following treatment. Epididymal fat pad weights were significantly reduced following combination therapy, however total body weight and liver weight were unchanged. Combination therapy increased the m RNA expression of Adipo R2, Ppar-α, Cpt1 a, Nrf-1 and Tfb2 m suggesting enhanced fatty acid oxidation and mitochondrial biogenesis. In addition, combination treatment resulted in increased catalase activity in Hfe^(-/-)mice. CONCLUSION Combination curcumin and vitamin E treatment decreases liver injury in this steatohepatitis model, indicating that combination therapy may be of value in NAFLD.展开更多
Background:Mixed partial thickness burns are the most common depth of burn injury managed at a large Australian paediatric hospital specialty burns unit.Prolonged time until re-epithelialisation is associated with inc...Background:Mixed partial thickness burns are the most common depth of burn injury managed at a large Australian paediatric hospital specialty burns unit.Prolonged time until re-epithelialisation is associated with increased burn depth and scar formation.Whilst current wound management approaches have benefits such as anti-microbial cover,these are not without inherent limitations including multiple dressing changes.The Biobrane^(■)RECELL^(■)Autologous skin Cell suspension and Silver dressings(BRACS)trial aims to identify the most effective wound management approach for mixed partial thickness injuries in children.Methods:All children presenting with an acute burn injury to the study site will be screened for eligibility.This is a single-centre,three-arm,parallel group,randomised trial.Children younger than 16 years,with burns≥5%total body surface area involving any anatomical location,up to 48 h after the burn injury,and of a superficial partial to mid-dermal depth,will be included.A sample size of 84 participants will be randomised to standard silver dressing or a Regenerative Epithelial Suspension(RES^(TM))with Biobrane^(■)or Biobrane^(■)alone.The first dressing will be applied under general anaesthesia and subsequent dressings will be changed every 3 to 5 days until the wound is≥95%re-epithelialised,with re-epithelialisation time the primary outcome.Secondary outcomes of acute pain,acute itch,scar severity,health-related quality of life,treatment satisfaction,dressing application ease and healthcare resource use will be assessed at each dressing change and 3,6 and 12 months post-burn injury.Discussion:The findings of this study can potentially change the wound management approach for superficial partial to mid-dermal burns in children locally and worldwide.Trial registration:The Australian New Zealand Clinical Trials Registry(ACTRN12618000245291)approved prospective registration on 15 February 2018.Registration details can be viewed at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374272&isReview=true.展开更多
文摘Tissue engineering allows the design of functionally active cells within supportive bio-scaffolds to promote the development of new tissues such as cartilage and bone for the restoration of pathologically altered tissues. However, all bone tissue engineering applications are limited by a shortage of stem cells. The adult bone marrow stroma contains a subset of nonhematopoietic cells referred to as bone marrow mesenchymal stem cells （BMSCs）. BMSCs are of interest because they are easily isolated from a small aspirate of bone marrow and readily generate singlecell-derived colonies. These cells have the capacity to undergo extensive replication in an undifferentiated state ex vivo. In addition, BMSCs have the potential to develop either in vitro or in vivo into distinct mesenchymal tissues,including bone, cartilage, fat, tendon, muscle, and marrow stroma. Thus, BMSCs are an attractive cell source for tissue engineering approaches. However, BMSCs are not homogeneous and the quantity of stem cells decreases in the bone marrow in aged population. A sequential loss of lineage differentiation potential has been found in the mixed culture of bone marrow stromal cells due to a heterogenous popu- lation. Therefore, a number of studies have proposed that homogenous bone marrow stem cells can be generated from clonal culture of bone marrow cells and that BMSC clones have the greatest potential for the application of bone regeneration in vivo.
基金supported by the Natural Science Foundation of China (81171470 and 81100761)the key clinical specialty discipline construction programme of Fujian, Chinathe Key Project of Science and Technology Bureau of Jiangsu Province (BL2013002)
文摘Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells （DPSCs） for potential application in tendon tissue engineering. The expression of tendon- related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid （PGA） fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a ootential stem cell source for tissue enEineerin~ of tendon-like tissue.
基金N.B.:IHBI ECR grant,Advance Queensland(AQ)Maternity Fund Award from the Queensland Government(DSITI),Young Researcher Award(2017-YR-RoW-9)from Lush(UK)supporting non-animal testing alternatives,National Health and Medical Research Council(NHMRC)Peter Doherty Early Career Research Fellowship(RF)(APP1091734)+5 种基金John Mills Young Investigator Award(YI0715)from the Prostate Cancer Foundation of Australia(PCFA)P.A.T.:Vice Chancellor’s RF(QUT)and AQ RF(QLD)J.A.C.:NHMRC PRFD.W.H.:Humboldt RF,ARC Industrial Transformation Training Center in Additive Biomanufacturing(IC160100026)NHMRC,World Cancer Foundation,National Breast Cancer Foundation,PCFA.D.W.H.,J.A.C.,C.C.N.:Movember Revolutionary Team Award(from Movember and PCFA).APCRC-Qthe Translational Research Institute are supported by grants from the Australian Government
文摘While stromal interactions are essential in cancer adaptation to hormonal therapies,the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood.Here,we tissue-engineered and validated an in vitro microtissue model of osteoblastic bone metastases,and used it to study the effects of androgen deprivation in this microenvironment.The model was established by culturing primary human osteoprogenitor cells on melt electrowritten polymer scaffolds,leading to a mineralized osteoblast-derived microtissue containing,in a 3D setting,viable osteoblastic cells,osteocytic cells,and appropriate expression of osteoblast/osteocyte-derived mRNA and proteins,and mineral content.Direct co-culture of androgen receptordependent/ independent cell lines (LNCaP,C4-2B,and PC3) led cancer cells to display functional and molecular features as observed in vivo.Co-cultured cancer cells showed increased affinity to the microtissues,as a function of their bone metastatic potential.Cocultures led to alkaline phosphatase and collagen-I upregulation and sclerostin downregulation,consistent with the clinical marker profile of osteoblastic bone metastases.LNCaP showed a significant adaptive response under androgen deprivation in the microtissues,with the notable appearance of neuroendocrine transdifferentiation features and increased expression of related markers (dopa decarboxylase,enolase 2).Androgen deprivation affected the biology of the metastatic microenvironment with stronger upregulation of androgen receptor,alkaline phosphatase,and dopa decarboxylase,as seen in the transition towards resistance.The unique microtissues engineered here represent a substantial asset to determine the involvement of the human bone microenvironment in prostate cancer progression and response to a therapeutic context in this microenvironment.
基金Supported by The National Health and Medical Research Council of Australiathe Lions Medical Research Foundation
文摘AIM To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on wholebody and hepatic fat oxidation of patients with nonalcoholic fatty liver disease(NAFLD).METHODS Participants were randomised into either circuit exercise training(EX;n = 13;3 h/wk without changes in dietary habits),or dietary energy restriction(ER) without changes in structured physical activity(ER;n = 8).Respiratory quotient(RQ) and whole-body fat oxidation rates(Fatox) were determined by indirect calorimetry under basal,insulin-stimulated and exercise conditions.Severity of disease and steatosis was determined by liver histology;hepatic Fatox was estimated from plasma β-hydroxybutyrate co.ncentrations;cardiorespiratory fitness was expressed as VO2 peak.Complete-case analysis was performed(EX:n = 10;ER:n = 6).RESULTS Hepatic steatosis and NAFLD activity score decreased with ER but not with EX.β-hydroxybutyrate concentrations increased significantly in response to ER(0.08 ± 0.02 mmol/L vs 0.12 ± 0.04 mmol/L,P = 0.03) but remained unchanged in response to EX(0.10 ± 0.03 mmol/L vs 0.11 ± 0.07 mmol/L,P = 0.39).Basal RQ decreased(P = 0.05) in response.to EX,while this change was not significant after ER(P = 0.38).VO_(2peak)(P < 0.001) and maximal Fa_(tox) during aerobic exercise(P = 0.03) improved with EX but not with ER(P > 0.05).The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis(r =-0.56,P = 0.04).CONCLUSION ER and EX lead to specific benefits on fat metabolism of patients with NAFLD.Increased hepatic Fat_(ox) in response to ER could be one mechanism through which the ER group achieved reduction in steatosis.
基金supported by a grant from the Australian Government
文摘Advanced prostate cancer(PCa)is known for its high prevalence to metastasize to bone,at which point it is considered incurable.Despite significant effort,there is no animal model capable of recapitulating the complexity of PCa bone metastasis.The humanized mouse model for PCa bone metastasis used in this study aims to provide a platform for the assessment of new drugs by recapitulating the human–human cell interactions relevant for disease development and progression.The humanized tissueengineered bone construct(hTEBC)was created within NOD-scid IL2rgnull(NSG)mice and was used for the study of experimental PC3-Luc bone metastases.It was confirmed that PC3-Luc cells preferentially grew in the hTEBC compared with murine bone.The translational potential of the humanized mouse model for PCa bone metastasis was evaluated with two clinically approved osteoprotective therapies,the non-species-specific bisphosphonate zoledronic acid(ZA)or the human-specific antibody Denosumab,both targeting Receptor Activator of Nuclear Factor Kappa-ΒLigand.ZA,but not Denosumab,significantly decreased metastases in hTEBCs,but not murine femora.These results highlight the importance of humanized models for the preclinical research on PCa bone metastasis and indicate the potential of the bioengineered mouse model to closely mimic the metastatic cascade of PCa cells to human bone.Eventually,it will enable the development of new effective antimetastatic treatments.
文摘We sought to evaluate central corneal thickness（CCT）,corneal endothelial cell density（ECD）and intraocular pressure（IOP）in patients with type 2 diabetes mellitus（DM）and to associate potential differences with diabetes duration and treatment modality in a prospective,randomized study.We measured ECD,CCT and IOP of125 patients with type 2 DM（mean age 57.1±11.5 years）and compared them with 90 age-matched controls.Measured parameters were analyzed for association with diabetes duration and glucose control modalities（insulin injection or oral medication）while controlling for age.In the diabetic group,the mean ECD（2511±252 cells/mm^2）,mean CCT（539.7±33.6μm）and mean IOP（18.3±2.5 mmHg）varied significantly from those the control group[ECD：2713±132 cells/mm^2（P〈0.0001）,CCT：525.0±45.3μm（P=0.003）and IOP：16.7±1.8 mmHg（P〈0.0001）].ECD was significantly reduced by about 32 cell/mm^2 for diabetics with duration of〉10 years when compared with those with duration of〈10 years（P〈0.05）.CCT was thicker and IOP was higher for diabetics with duration of〉10 years than those with duration of〈10 years（P〉0.05）.None of the measured parameters was significantly associated with diabetes duration and treatment modality（P〉0.05）.In conclusion,subjects with type 2DM exhibit significant changes in ECD,IOP and CCT,which,however,are not correlated with disease duration or if the patients receive on insulin injection or oral medications.
基金the Research Centre, College of Applied Medical Sciences and the Deanship of Scientific Research at King Saud University for funding this research
文摘AIM: To investigate the number of hypertensive patients, the optometrist is able to identify by routinely taking blood pressure(BP) measurements for patients in "at-risk" groups, and to sample patients’ opinions regarding in-office BP measurement. Many of the optometrists in Saudi Arabia practice in optical stores.These stores are wide spread, easily accessible and seldom need appointments. The expanding role of the optometrist as a primary health care provider(PHCP) and the increasing global prevalence of hypertension,highlight the need for an integrated approach towards detecting and monitoring hypertension.METHODS: Automated BP measurements were made twice(during the same session) at five selected optometry practices using a validated BP monitor(Omron M6) to assess the number of patients with high BP(HBP)- in at-risk groups-visiting the eye clinic routinely. Prior to data collection, practitioners underwent a two-day training workshop by a cardiologist on hypertension and how to obtain accurate BP readings. A protocol for BP measurement was distributed and retained in all participating clinics. The general,,.,attitude towards cardiovascular health of 480 patients aged 37.2(±12.4)y and their opinion towards in-office BP measurement was assessed using a self-administered questionnaire.RESULTS: A response rate of 83.6% was obtained for the survey. Ninety-three of the 443 patients(21.0%)tested for BP in this study had HBP. Of these,(62subjects) 67.7% were unaware of their HBP status. Thirty of the 105 subjects(28.6%) who had previously been diagnosed with HBP, still had HBP at the time of this study, and only 22(73.3%) of these patients were on medication. Also, only 25% of the diagnosed hypertensive patients owned a BP monitor.CONCLUSION: Taking BP measurements in optometry practices, we were able to identify one previously undiagnosed patient with HBP for every 8 adults tested.We also identified 30 of 105 previously diagnosed patients whose BP was poorly controlled, twenty-two of whom were on medication. The patients who participated in this study were positively disposed toward the routine measurement of BP by optometrists.
基金Supported by the Research Centre,College of Applied Medical Sciences and the Deanship of Scientific Research at King Saud University
文摘AIM： To examine the prevalence of dyslexia and Meares-Irlen syndrome（MIS） among female students and determine their level of visual stress in comparison with normal subjects.·METHODS： A random sample of 450 female medical students of King Saud University Riyadh（age range, 18-30y） responded to a wide range of questions designed to accomplish the aims of this study. The detailed questionnaire consisted of 54 questions with 12 questions enquiring on ocular history and demography of participants while 42 questions were on visual symptoms. Items were categorized into critical and non-critical questions（CQ and NCQ） and were rated on four point Likert scale. Based on the responses obtained, the subjects were grouped into normal（control）, dyslexic with or without MIS（Group 1） and subjects with MIS only（Group 2）. Responses were analysed as averages and mean scores were calculated and compared between groups using one way analysis of variance to evaluate total visual stress score（TVSS =NCQ ＋CQ）, critical and non-critical visual stress scores. The relationship between categorical variables such as age, handedness and condition were assessed with Chi-square test.·RESULTS： The completion rate was 97.6% and majority of the respondents（92%） were normal readers, 2%dyslexic and 6% had MIS. They were age-matched. More than half of the participants had visited an eye care practitioner in the last 2y. About 13% were recommendedeye exercises and one participant experienced pattern glare. Hand preference was not associated with any condition but Group 1 subjects（3/9, 33%） were significantly more likely to be diagnosed of lazy eye than Group 2（2/27, 7%） and control（27/414, 7%） subjects. The mean±SD of TVSS responses were 63±14 and it was 44±9for CQ and 19 ±5 for NCQ. Responses from all three variables were normally distributed but the CQ responses were on the average more positive（82%） in Group 2 and less positive（46%） in Group 1 than control. With NCQ,the responses were equally less positive in Group 1 and2 than control. Group 2 subjects showed significantly higher TVSS（P =0.002）, NCQ（P =0.006） and CQ（P =0.008）visual stress scores than control but no difference between Group 1 and control subjects, was observed for all scores（P 〉0.05, for all comparisons）.·CONCLUSION： The prevalence of dyslexia and MIS among Saudi female students was 2% and 6%,respectively. Critical questions performed best for assessing visual stress symptoms in dyslexic and MIS subjects. Generally, students with MIS were more sensitive to visual stress than normal students but dyslexics were more likely to present with a lazy eye than MIS and normal readers.
文摘This study compared proximal femoral morphology in patients living in soft and hard water regions. The proximal femoral morphology of two groups of 70 patients living in hard and soft water regions with a mean age of 72.29 (range: 50 to 87 years) was measured using an antero-posterior radiograph of the non-operated hip with magnification adjusted. The medullary canal diameter at the level of the lesser trochanter (LT) was significantly wider in patients living in the hard water region (mean width: 1.9 mm wider;p = 0.003). No statistical significant difference was found in the medullary canal width at 10 cm below the level of LT, Dorr index, or Canal Bone Ratio (CBR). In conclusion, the proximal femoral morphology does differ in patients living in soft and hard water areas. These results may have an important clinical bearing in patients undergoing total hip replacement surgery. Further research is needed to determine whether implant survivorship is affected in patients living in hard and soft water regions.
文摘Large scale exome sequencing studies have ＇revealed regions of the genome, which contribute to the castrate resistant prostate cancer （CRPC） phenotype.1-3 Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor （AR） and speckle-type POZ protein （SPOP） genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al.4 which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particnlarly in the context of SPOP-mediated degradation of the AR.
基金supported by the Gong-Yi Program of Ministry of Environmental Protection(201209008)the Open Funds of Key Lab of Climate and Health of Shanghai(QXJK201205)
文摘Objective To study the relation between temperature and mortality by estimating the temperature-related mortality in Beijing, Shanghai, and Guangzhou. Methods Data of daily mortality, weather and air pollution in the three cities were collected. A distributed lag nonlinear model was established and used in analyzing the effects of temperature on mortality. Current and future net temperature-related mortality was estimated. Results The association between temperature and mortality was J-shaped, with an increased death risk of both hot and cold temperature in these cities. The effects of cold temperature on health lasted longer than those of hot temperature. The projected temperature-related mortality increased with the decreased cold-related mortality. The mortality was higher in Guangzhou than in Beijing and Shanghai. Conclusion The impact of temperature on health varies in the 3 cities of China, which may have implications for climate policy making in China.
文摘It is believed that human ancestors evolved the ability to run bipedally approximately 2 million years ago. This form of locomotion may have been important to our survival and likely has influenced the evolution of our body form. As our bodies have adapted to run, it seems unusual that up to 79% of modern day runners are injured annually. The etiology of these injuries is clearly multifactorial. However, 1 aspect of running that has significantly changed over the past 50 years is the footwear we use. Modern running shoes have become increasingly cushioned and supportive, and have changed the way we run. In particular, they have altered our footstrike pattern from a predominantly forefoot strike(FFS) landing to a predominantly rearfoot strike(RFS) landing. This change alters the way in which the body is loaded and may be contributing to the high rate of injuries runners experience while engaged in an activity for which they were adapted. In this paper, we will examine the benefits of barefoot running(typically an FFS pattern),and compare the lower extremity mechanics between FFS and RFS. The implications of these mechanical differences, in terms of injury, will be discussed. We will then provide evidence to support our contention that FFS provides an optimal mechanical environment for specific foot and ankle structures, such as the heel pad, the plantar fascia, and the Achilles tendon. The importance of footwear will then be addressed, highlighting its interaction with strike pattern on mechanics. This analysis will underscore why footwear matters when assessing mechanics. Finally, proper preparation and safe transition to an FFS pattern in minimal shoes will be emphasized. Through the discussion of the current literature, we will develop a justification for returning to running in the way for which we were adapted to reduce running-related injuries.
基金funded by the TPCH foundation grant (MS201140)the RBWH foundation grant 2012+1 种基金funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP1099452)funded in part by a Practitioner Fellowship (APP1117065) from the National Health and Medical Research Council of Australia
文摘Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.
文摘High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the healing of bone fractures, and vice versa. Despite this knowledge, most impact trauma studies in animals have focussed on bone fractures or soft tissue trauma in isolation. However, given the simultaneous impact on both tissues a better understanding of the interaction between these two injuries is necessary to optimise clinical treatment. The aim of this study was therefore to develop a new experimental model and characterise, for the first time, the healing of a complex fracture with concurrent closed soft tissue trauma in sheep. A pendulum impact device was designed to deliver a defined and standardised impact to the distal thigh of sheep, causing a reproducible contusion injury to the subcutaneous soft tissues. In a subsequent procedure, a reproducible femoral butterfly fracture (AO C3-type) was created at the sheep’s femur, which was initially stabilised for 5 days by an external fixator construct to allow for soft tissue swelling to recede, and ultimately in a bridging construct using locking plates. The combined injuries were applied to twelve sheep and the healing observed for four or eight weeks (six animals per group) until sacrifice. The pendulum impact led to a moderate to severe circumferential soft tissue injury with significant bruising, haematomas and partial muscle disruptions. Posttraumatic measurements showed elevated intra-compartmental pressure and circulatory tissue breakdown markers, with recovery to normal, pre-injury values within four days. Clinically, no neurovascular deficiencies were observed. Bi-weekly radiological analysis of the healing fractures showed progressive callus healing over time, with the average number of callus bridges increasing from 0.4 at two weeks to 4.2 at eight weeks. Biomechanical testing after sacrifice showed in- creasing torsional stiffness between four and eight weeks healing time from 10% to 100%, and increasing ultimate torsional strength from 10% to 64% (relative to the contralateral control limb). Our results demonstrate the robust healing of a complex femur fracture in the presence of a severe soft tissue contusion injury in sheep and demonstrate the establishment of a clinically relevant experimental model, for research aimed at improving the treatment of bone fractures accompanied by closed soft tissue injuries.
文摘Background:Overweight and obesity has become a serious public health problem in many parts of the world.Studies suggest that making small changes in daily activity levels such as"breaking-up"sedentary time(i.e.,standing)may help mitigate the health risks of sedentary behavior.The aim of the present study was to examine time spent in standing(determined by count threshold),lying,and sitting postures(determined by inclinometer function)via the ActiGraph GT3X among sedentary adults with differing weight status based on body mass index(BMI)categories.Methods:Participants included 22 sedentary adults(14 men,8 women;mean age 26.5±4.1 years).All subjects completed the self-report International Physical Activity Questionnaire to determine time spent sitting over the previous 7 days.Participants were included if they spent seven or more hours sitting per day.Postures were determined with the ActiGraph GT3X inclinometer function.Participants were instructed to wear the accelerometer for 7 consecutive days(24 h a day).BMI was categorized as:18.5 to【25 kg/m2as normal,25 to【30 kg/m2as overweight,and≥30 kg/m2as obese.Results:Participants in the normal weight(n=10)and overweight(n=6)groups spent significantly more time standing(after adjustment for moderate-to-vigorous intensity physical activity and wear-time)(6.7 h and 7.3 h respectively)and less time sitting(7.1 h and 6.9 h respectively)than those in obese(n=6)categories(5.5 h and 8.0 h respectively)after adjustment for wear-time(p【0.001).There were no significant differences in standing and sitting time between normal weight and overweight groups(p=0.051 and p=0.670 respectively).Differences were not significant among groups for lying time(p=0.55).Conclusion:This study described postural allocations standing,lying,and sitting among normal weight,overweight,and obese sedentary adults.The results provide additional evidence for the use of increasing standing time in obesity prevention strategies.
文摘Background： It has been reported that strenuous exercise increases the number of bone marrow-derived progenitor cells such as CD34＋ cells in the blood, but no previous studies have investigated the changes in circulating CD34＋ cells following resistance exercise. This study tested the hypothesis that the number of CD34＋ cells in the blood would increase after eccentric exercise of the elbow flexors, but decrease in recovery, and the magnitude of the changes would be dependent on the magnitude of muscle damage. Methods： Nine men （28.0 ± 6.6 years） performed exercises consisting of 10 sets of six maximal voluntary eccentric contractions of the elbow flexors with their non-dominant arm. Six of them performed the same exercise with the same ann 4 weeks later. Changes in indirect markers of muscle damage were measured before, within 10 min after, and at 24, 48, 72, and 96 h after eccentric exercise. Differential leukocyte counts （total leukocytes, neutrophils, lymphocytes, monocytes） and CD34＋ cells in the blood were measured before, immediately after, and at 2, 24, 48, 72, and 96 h following the exercises. Results： After eccentric exercise, significant （p 〈 0.05） decreases in maximal voluntary isometric contraction torque and increases in delayed onset muscle soreness and plasma creatine kinase activity were observed. However, no significant changes in leukocytes and CD34＋ cells were evident. The changes in muscle damage markers were significantly （p 〈 0.05） smaller following the second exercise session as compared with the first exercise session, but the changes in leukocytes and CD34＋ cells were not significantly different between sessions. Conclusion： These results did not support the hypothesis, and showed that eccentric exercise-induced muscle damage to the elbow flexors did not influence the number of circulating CD34＋ cells.
文摘AIM To investigate the synergistic hepato-protective properties of curcumin and vitamin E in an Hfe^(-/-)high calorie diet model of steatohepatitis.METHODS Hfe^(-/-)C57BL/6J mice were fed either a high calorie diet or a high calorie diet with 1 mg/g curcumin; 1.5 mg/g vitamin E; or combination of 1 mg/g curcumin + 1.5 mg/g vitamin E for 20 wk. Serum and liver tissue were collected at the completion of the experiment. Liver histology was graded by a pathologist for steatosis, inflammation and fibrosis. RNA and protein was extracted from liver tissue to examine gene and protein expression associated with fatty acid oxidation, mitochondrial biogenesis and oxidative stress pathways.RESULTS Hfe^(-/-)mice fed the high calorie diet developed steatohepatitis and pericentral fibrosis. Combination treatment with curcumin and vitamin E resulted in a greater reduction of percent steatosis than either vitamin E or curcumin therapy alone. Serum alanine aminotransferase and non-alcoholic fatty liver disease(NAFLD) activity score were decreased following combination therapy with curcumin and vitamin E compared with high calorie diet alone. No changes were observed in inflammatory or fibrosis markers following treatment. Epididymal fat pad weights were significantly reduced following combination therapy, however total body weight and liver weight were unchanged. Combination therapy increased the m RNA expression of Adipo R2, Ppar-α, Cpt1 a, Nrf-1 and Tfb2 m suggesting enhanced fatty acid oxidation and mitochondrial biogenesis. In addition, combination treatment resulted in increased catalase activity in Hfe^(-/-)mice. CONCLUSION Combination curcumin and vitamin E treatment decreases liver injury in this steatohepatitis model, indicating that combination therapy may be of value in NAFLD.
基金supported by an Australian National Health and Medical Research Council administered fellowship(#1161138).
文摘Background:Mixed partial thickness burns are the most common depth of burn injury managed at a large Australian paediatric hospital specialty burns unit.Prolonged time until re-epithelialisation is associated with increased burn depth and scar formation.Whilst current wound management approaches have benefits such as anti-microbial cover,these are not without inherent limitations including multiple dressing changes.The Biobrane^(■)RECELL^(■)Autologous skin Cell suspension and Silver dressings(BRACS)trial aims to identify the most effective wound management approach for mixed partial thickness injuries in children.Methods:All children presenting with an acute burn injury to the study site will be screened for eligibility.This is a single-centre,three-arm,parallel group,randomised trial.Children younger than 16 years,with burns≥5%total body surface area involving any anatomical location,up to 48 h after the burn injury,and of a superficial partial to mid-dermal depth,will be included.A sample size of 84 participants will be randomised to standard silver dressing or a Regenerative Epithelial Suspension(RES^(TM))with Biobrane^(■)or Biobrane^(■)alone.The first dressing will be applied under general anaesthesia and subsequent dressings will be changed every 3 to 5 days until the wound is≥95%re-epithelialised,with re-epithelialisation time the primary outcome.Secondary outcomes of acute pain,acute itch,scar severity,health-related quality of life,treatment satisfaction,dressing application ease and healthcare resource use will be assessed at each dressing change and 3,6 and 12 months post-burn injury.Discussion:The findings of this study can potentially change the wound management approach for superficial partial to mid-dermal burns in children locally and worldwide.Trial registration:The Australian New Zealand Clinical Trials Registry(ACTRN12618000245291)approved prospective registration on 15 February 2018.Registration details can be viewed at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374272&isReview=true.
